Terms in this set (514)
Describe the Epidemiology of Acute Laryngotracheobronchitis?Age of Incidence: 3 months - 5 years Peak Incidence: 2 years Sex Incidence: Males Seasonal Incidence: Cold Days Recurrence: 3-6 years, decrease with growthWhat is the main etiological agent for Acute Laryngotracheobronchitis?Parainfluenza Virus - 75% of casesWhat virus has been associated with severe Laryngotracheobronchitis?Influenzae ADescribe the Clinical Manifestations of Acute Laryngotracheobronchitis?1. Acute fulminating course of high fever, sore throat, dyspnea, and rapidly progressing respiratory obstruction. 2. Most have a URTI with rhinorrhea, pharyngitis, mild cough, and low grade fever. 3. Barking Cough, hoarseness, and inspiratory stridor. 4. Symptoms are worse at night. 5. Agitation and crying aggravate signs and symptoms.Describe the Physical Examination of Acute Laryngotracheobronchitis?1. Hoarse voice, coryza, normal to moderately inflamed pharynx, and slightly increased respiratory rate.This is a disease of the upper airway, and alveolar gas exchange is usually normal?CroupHypoxia and low oxygen saturation are seen only when?Complete Airway Obstruction is imminentA child who is hypoxic, cyanotic, pale, or obtunded needs this treatment?Immediate Airway ManagementThis is a clinical diagnosis and does not require a radiograph of the neck?CroupThe radiograph of the neck will show this in Acute Laryngotracheobronchitis?Subglottic Narrowing or Steeple Sign on PA -Can be present in patients with epiglottitis.What is the main complication of Acute Laryngotracheobronchitis?Extension of the infectious process to other regions of the respiratory tract such as the middle ear, terminal bronchioles, or pulmonary parenchyma.This condition may be a complication of viral croup rather than a distinct disease?Bacterial TracheitisWhat is the mainstay treatment of Croup?Airway ManagementWhat are the beneficial effects of Cold Mist?1. Moistens airway secretions to facilitate clearance. 2. Soothes inflamed mucosa. 3. Provides comfort and reassurance to the child, lessening anxiety.Children with both Wheezing and Croup may experience this when given Cold Mist?Worsening of their BronchospasmThe marked decrease in the need for tracheostomies in croup has been attributed to what treatment?Nebulized EpinephrineWhat is the MOA of Nebulization?Constriction of the precapillary arterioles through the alpha adrenergic receptors causing fluid resorption from the interstitial space and a decrease in the laryngeal mucosal edema.What are the indications for the administration of Nebulized Epinephrine?1. Moderate to severe stridor at rest. 2. Need for intubation. 3. Respiratory distress. 4. Hypoxia. 5. When stridor doesn't respond to cool mist.In what conditions should Nebulized Epinephrine be used cautiously?1. Tachycardic heart seen in Tetralogy of Fallot 2. Vesicular Outlet ObstructionFor a patient that was treated for croup, under what conditions can they go home?1. No stridor at rest. 2. Normal air entry. 3. Normal color. 4. Normal level of consciousness. 5. Received steroids.What are the benefits of giving steroids (corticosteroids) to a patient with croup?Decrease the edema in the laryngeal mucosa through their anti-inflammatory action. 1. Reduced hospitalization. 2. Shorter duration of hospitalization. 3. Reduced need for subsequent interventions such as epinephrine administration.These two treatments have an equivalent effect in treating croup?1. Intramuscular Dexamethasone 2. Nebulized BudesonideWhat is the only adverse effect in the treatment of croup with Corticosteroids?Candida albicans laryngotracheitis in a patient who received dexamethasone.Corticosteroids should not be administered to children with these conditions?1. Varicella 2. TuberculosisThis treatment has shown similar clinical improvements in children with croup when compared with responses in children given racemic epinephrine?HelioxWhen is hospitalization for children with croup indicated?1. Progressive stridor 2. Severe stridor at rest 3. Respiratory distress 4. Hypoxia 5. Cyanosis 6. Depressed mental status 7. Need for reliable observationWhat causes most death in patients with croup?Laryngeal Obstruction or Complications of TracheotomyWhat is the Epidemiology of Acute Epiglottitis (Supraglottitis)?Incidence: 2-4 years old Currently: Adult with a Sore Throat -Underimmunized ChildrenIn the past what was the most common identified etiology of Acute Epiglottitis?Hemophilus Influenzae Type BWhat are other agents that cause Acute Epiglottitis?1. Streptococcus pyogenes 2. S. pneumoniae 3. Staphylococcus aureusDescribe the Morphology of Hemophilus Influenzae type B?Small, pleomorphic, gram (-) rods.Describe the Morphology of Streptococcus pyogenes?1. Gram (+) Coccoid-shaped in chains. 2. Large zones of Beta Hemolysis. 3. Produce capsules composed of hyaluronic acid (role in virulence). 4. Hair-like pili, consist of M protein and covered by lipoteichoic acid. 5. Major Virulence Factor is M protein.Describe the Morphology of Streptococcus pneumoniae?1. Encapsulated, gram (+) cocci, catalase negative, and alpha hemolytic. 2. Lancet-shaped, singly, in pairs, or in short chains. 3. Quellung reaction or capsular precipitation reaction most useful for identification of S. pneumoniae. 4. When optochin placed on agar dish, growth will be inhibited. 5. Bile solubility.What two laboratory tests are important for identification of pneumococcus?1. Quellung Reaction or Capsular Precipitation Reaction. 2.Optochin Sensitivity.What determined the virulence of S. pneumoniae?Capsular AntigensWhat are the toxins produced by S. pneumoniae?1. Pneumolysin O - A hemolysin cytolytic for eukaryotic cells that have cholesterol as a component of their cell membrane. 2. Autolysin: Facilitates release of pneumolysin and other toxic proteins or inflammatory substances.What is the major pathogen for humans?Staphylococcus aureusDescribe the Morphology of S. aureus?1. Gram (+) spherical cells, arranged in grape-like clusters and is coagulase (+). 2. Non-motile, do not form spores. 3. Forms grey to deep golden yellow colonies. 4. Ferments carbohydrates producing lactic acid. 5. Resistant to drying, heat. 6. Antigenic Structures: Peptidoglycan, Teichoic Acid, Protein A.What are the Clinical Manifestations of Acute Epiglottitis1. Sore throad and fever. 2. In hours, patient appears toxic, swallowing is difficult, and breathing is labored. 3. Drooling often present. 4. Neck hyperextended to maintain airway. 5. Brief period of airway hunger with restlessness followed by rapidly increasing cyanosis and coma. 6. Stridor is a late finding suggesting near-complete airway obstruction. 7. Barking cough is rare. 8. Usually no other family members are ill with acute respiratory symptoms.For what condition will a child assume a tripod position sitting upright and leaning forward with the chin up and mouth open while bracing on the arms?Acute EpiglottitisUpon Laryngoscopy, visualization of this is seen for Acute Epiglottitis?"Cherry Red" Swollen Epiglottis -Aryepiglottic folds may be more involved than epiglottis itself.Anxiety provoking interventions such as what should be avoided in the patient until airway is secure?1. Phlebotomy 2. Intravenous Line Placement 3. Placing the Child Supine 4. Direct inspection of the oral cavityClassic Radiographs of a child who has Acute Epiglottitis shows?Thumb SignWhat are the complications of Acute Epiglottitis?1. Concomitant Bacteremia 2. Also pneumonia, cervical lymphadenitis, otitis media. 3. Meningitis, arthritis, and other invasive infections with H. influenzae type B rare.What is the Treatment for Acute Epiglottitis?1. Establish airway by nasotracheal intubation or tracheostomy. -Respiratory distress and cyanosis should disappear. 2. Ceftriaxone, Cefotaxime or Ampicillin + Sulbactam given parenterally pending culture and susceptibility reports.This is a medical emergency and warrants immediate treatment?EpiglottitisWhat are ineffective treatments for Acute Epiglottitis?1. Racemic Epinephrine 2. CorticosteroidsAt the time of airway stabilization, what other diagnostic procedures should be done for Acute Epiglottitis?1. Cultures of Blood 2. Epiglottic Surface 3. Cerebrospinal FluidWhen is Chemoprophylaxis for household contacts of a patient not recommended?1. If the child is younger than 48 months. 2. If child has not completed the HiB immunization series.What should be given to all household members if there is one contact younger than 48 months who is incompletely immunized or an immunocompromised child?Rifampicin ProphylaxisWhat is the mortality rate of untreated epiglottitis?6%What is the Epidemiology of Spasmodic Croup?Incidence: 1 - 3 years oldSpasmodic Croup is clinically similar to acute laryngotracheobronchitis except for this finding?Infection is absent in patient and family of a patient with spasmodic croup.What is the etiology of Spasmodic Croup?1. Viral in some cases. 2. Allergic and Psychological Factors in others.What are the clinical manifestations of Spasmodic Croup?1. Occur more frequently in evening or night. 2. May be preceded with mild to moderate coryza and hoarseness. 3. Barking, metallic cough. 4. Noisy inspiration, respiratory distress, anxious, and frightened. 5. Usually afebrile. 6. May represent more of an allergic reaction to viral antigens than direct infection. 7. Recur several times.What does the Laryngoscopy of a patient with Spasmodic Croup reveal?Pale, watery edema, with preservation of the epithelium.What does the laryngoscopy of a patient with Acute Laryngotracheobronchitis reveal?Erythematous edema and destruction of the epithelium.What is the mainstay treatment of Spasmodic Croup?1. Airway Management. -Can improve rapidly without treatment.What is the principal site of obstruction for Acute Infectious Laryngitis?Subglottic AreaWhat is the Etiology of Acute Infectious Laryngitis?VirusesWhat are the Clinical Manifestations of Acute Infectious Laryngitis?1. Onset of URTI with sore throat, cough, and hoarseness. 2. Generally mild. 3. Respiratory distress for young infants usually. 4. Hoarseness and loss of voice out of proportion to systemic signs and symptoms.What does the PE of a patient with Acute Infectious Laryngitis reveal?Pharyngeal InflammationWhat does a Laryngoscopy of a patient with Acute Infectious Laryngitis reveal?Inflammatory edema of the vocal cords and subglottic tissue.This is an acute bacterial infection of the upper airway, it does not involve the epiglottis, but is capable of causing life-threatening airway obstruction?Bacterial TracheitisWhat is the Epidemiology of Bacterial Tracheitis?Incidence: < 3 years old. Sex: No clear differences. Often follows a viral respiratory infection, considered bacterial complication.What is the most common etiologic agent of Bacterial Tracheitis?Staphylococcus aureusWhat are other etiologic agents of Bacterial Tracheitis?1. S. aureus 2. Moraxella catarrhalis 3. Nontypeable H. influenzae 4. Anaerobic OrganismsDescribe the Morphology of Moraxella Catarrhalis?1. Non-motile, nonfermentative, and oxidase positive. 2. Small, gram (-) bacilli, coccobacilli, or cocci. 3. Produces beta lactamase. 4. Produces non pigmented or pinkish gray opaque colonies.Describe the Morphology of Anaerobic Bacteria?1. Obtain energy from fermentation reactions. 2. Require reduced oxygen tension for growth.What are the Clinical Manifestations of Bacterial Tracheitis?1. Brassy Cough, part of viral laryngotracheobronchitis. 2. High fever and toxicity with respiratory distress. 3. Can lie flat. 4. Does not drool. 5. Does not have the dysphagia associated with epiglottitis.What is the main pathologic feature of Bacterial Tracheitis?Mucosal swelling at the level of the cricoid cartilage, accompanied by copious thick, purulent secretions, sometimes causing pseudomembranes.How is the Diagnosis of Bacterial Tracheitis confirmed?Evidence of bacterial upper airway disease which includes high fever, purulent airway secretions, and absence of classic findings of epiglottitis.What is the treatment for Bacterial Tracheitis?1. Antimicrobial Therapy (Anti-Staphylococcus Agents). 2. Artificial Airway if diagnosis confirmed. 3. Supplemental oxygen may be necessary. -Racemic Epinephrine is ineffective.What are the Complications of Bacterial Tracheitis?1. Patchy infiltrates and focal densities seen in chest roentgenograms. 2. Subglottic narrowing and a rough-ragged tracheal air column. 3. If airway management is not optimal, cardiorespiratory arrest can occur. 4. Toxic Shock Syndrome.What lymph nodes drain the mucosal surface of the upper airway and digestive tract?1. Retropharyngeal Nodes 2. Lateral Pharyngeal NodesWhere do the nodes lie?1. Within the retropharyngeal space (between pharynx and cervical vertebrae extending down into superior mediastinum). 2. Lateral pharyngeal space (bounded by pharynx medially, carotid sheath posteriorly, and muscle of styloid laterally) which are interconnected.This type of abscess can result from penetrating trauma to the oropharynx, dental, and vertebral osteomyelitis?Retropharyngeal AbscessInfection in the retropharyngeal and lateral pharyngeal spaces can result in this?Airway Compromise or Posterior MediastinitisWhat is the epidemiology of Retropharyngeal Abscess?Incidence: < 3 - 4 years old. Sex Incidence: Higher in MalesWhy are Retropharyngeal Abscesses much less common in older children and adults?The retropharyngeal nodes involute after 5 years of age.What is the main etiology of Retropharyngeal Abscess?PolymicrobialWhat are the usual pathogens of Retropharyngeal Abscess?1. Group A Streptococcus 2. Oropharyngeal Anaerobic Bacteria 3. Staphylococcus aureus 4. Haemophilus influenzae 5. Klebsiella 6. Mycobacterium avium-intracellulareDescribe the Morphology of Klebsiella pneumoniae?1. Small, gram (-), non-spore forming rods. 2. Friedlander's bacillus. 3. Lactose fermenting, non-motile. 4. Large capsule causes colonites to appear large, moist, and mucoid. 5. Presence of O and K antigenWhat are the Clinical Manifestations of Retropharyngeal Abscess?1. Fever, irritability, decreased oral intake, and drooling. 2. Neck stiffness, torticollis, and refusal to move the neck. 3. Talking child may complain of sore throat and neck pain. 4. Muffled voice, stridor, and respiratory distress.What does the PE of Retropharyngeal Abscess reveal?1. Bulging of the posterior pharyngeal wall, which is present in less than 50% of infants. 2. Cervical Lymphadenopathy.What provides the Definitive Diagnosis of Retropharyngeal Abscess?Incision for drainage and culture of abscessed node.What imaging modality can be useful in identifying the presence of retropharyngeal abscess?CT ScanWhat is the treatment of Retropharyngeal Abscess?1. Intravenous Antibiotics with or without surgical drainage. 2.A 3rd generation Cephalosporin + Ampicillin-sulbactam or Clindamycin. 3. Drainage if respiratory distress or failure to improve with intravenous antibiotic treatment.What are the complications of Retropharyngeal Abscess?1. Significant Upper Airway Obstruction 2. Rupture leading to Aspiration Pneumonia 3. Extension of Mediastinum 4. Thrombophlebitis of the Internal Jugular Vein 5. Erosion of the Carotid Artery SheathDescribe Short-Acting B-Adrenergic Receptor Agonists?1. For acute inhalation or oral treatment of bronchospasm, "reliever drugs." 2. Onset of action of 1-5 minutes lasting 2-6 hours. 3. Topical application through aerosols, which produce high local concentrations in the lungs with low systemic delivery, improving therapeutic ratio by minimizing systemic side effects.Describe Terbutaline?1. Maximum plasma concentration within 3 hours. 2. First metabolism in intestinal wall and liver. 3. Bioavailability = 10%. 4. Metabolized by conjugation with sulfuric acid and excreted as sulfate conjugate.Describe Albuterol?1. Inhaled, 10-20% reaches lower airways. 2. Remainder is retained in delivery system or deposited in oropharynx where it's swallowed. 3. Fraction deposited in airways is absorbed into pulmonary tissues and circulation. 4. In systemic circulation it becomes accessible to hepatic metabolism and excreted in urine as unchanged drug and as phenolic sulphate (inactive metabolite).Describe Long-Acting B-Adrenergic Receptor Agonists such as Salmeterol?1. Bronchodilation for over 12 hours. 2. Extended side chain make it more lipophilic than albuterol. 3. Lipophilicity regulates the diffusion rate away from the receptor by determining the degree of partitioning in lipid bilayer of the membrane.What are the Adverse Effects of B-Adrenergic Receptor Agonists?1. Increased Heart Rate 2. Cardiac Arrythmias 3. CNS Effects: Headaches, sleep disturbances, agitation, hyperactivity, and restlessness. 4. Skeletal Muscle Tremors 5. Muscle Cramps 6. Metabolic Disorders: Increased glucose, lactate, and free fatty acids in plasma - In DM, hyperglycemia may worsen. 7. Hypersensitivity Reactions: Angioedema, urticaria, bronchospasm, hypotension, and collapse.What is the use of Steroids in treatment of Asthma?Potent and broad anti-inflammatory efficacy.What are the routes of administration of steroids?1. Parenteral and Oral Corticosteroids most beneficial in acute illness. 2. Inhaled Corticosteroids for long term control.What is the MOA of Steroids?1. Effective in inhibiting airway inflammation due to the following events -- 2. Modulation of cytokine and chemokine production. 3. Inhibition of eicosanoid synthesis. 4. Inhibition of accumulation of basophils, eosinophils, and other leukocyte in the lung tissue. 5. Decreased vascular permeability.What drug is used for treatment of transplant rejection and autoimmune disorders?1. Prednisone 2. Prednisolone 3. Other Glucocorticoids w/ Immunosuppressive AgentsWhat is the MOA of Adrenocortical Steroids?1. Steroids lyse and induce redistribution of lymphocytes, causing rapid, transient decrease in peripheral blood lymphocyte counts. 2. Broad anti inflammatory effects on cellular immunity. 3. Little effect on humoral immunity. 4. Downregulation of proinflammatory cytokines such as IL-1 and IL-6. 5. T cells are inhibited from making IL-2. 6. Activation of cytotoxic T cells inhibited. 7. Neutrophils and monocytes display poor chemotaxis and decreased lysosomal enzyme release.This is used to reverse acute transplant rejection and acute exacerbation of selected autoimmune disorders?Intravenous Methylprednisolone Sodium Succinate (SOLU-MEDROL, A-METHAPRED).What are the Therapeutic Uses of Adrenocortical Steroids (Glucocorticoids)?1. Prevent and treat transplant rejection. 2. Treatment of graft-versus-host disease in bone-marrow transplantation. 3. To treat rheumatoid arthritis, SLE, systemic dermatomyositis, psoriasis, asthma, inflammatory bowel disease, inflammatory ophthalmic diseases, autoimmune hematologic disorders, and acute exacerbations of multiple sclerosis. 4. Limit allergic reactions that occur with other immunosuppressive agents that are used in transplant recipients to block first-dose cytokine storm caused by treatment with muromonab-CD3.What are the Toxic effects of Adrenocortical Steroids?1. Growth Retardation 2. Avascular Necrosis of Bone 3. Osteopenia 4. Increased Risk of Infection 5. Poor Wound Healing 6. Cataracts 7. Hyperglycemia 8. HypertensionThe concomitant therapy of glucocorticoids plus this has allowed a reduction in the dosages of steroids administered?CyclosporineWhat are the most common effects with systemic corticosteroid treatment that lasts for only 5-10 days?1. Mood Disturbances 2. Increased Appetite 3. Loss of Glucose Control in Diabetes 4. CandidiasisWhich agents inhibit antigen-induced bronchospasm as well as prevent the release of histamine from sensitized mast cells?Mast Cell-Stabilizing AgentsWhat is the MOA of Cromolyn Sodium and Nedocromil Sodium, the Mast-Cell-Stabilizing Agents?1. Inhibiting mediator release from bronchial mast cells. 2. An ability to reverse increased functional activation in leukocytes. 3. Suppression of the activating effects of chemotactic peptides on human neutrophils, eosinophils, and monocytes. 4. Inhibition of parasympathetic and cough reflexes. 5. Inhibition of leukocyte trafficking is asthmatic airways.Describe the Pharmacokinetic Properties of Mast-Cell Stabilizers?1. Only 1% of oral dose is absorbed. 2. Excreted unchanged in urine and bile. 3. Peak concentration within 15 minutes. 4. Half life of 45-100 minutes.What are the Toxic effects of Mast-Cell Stabilizers?1. Bronchospasm 2. Coughing 3. Wheezing 4. Laryngeal Edema 5. Joint Swelling and Pain 6. Angioedema 7. Headache 8. Rash 9. Nausea 10. Bad Taste -Adverse reactions are infrequent and minor. -Ineffective in treating ongoing bronchoconstriction.What are the Therapeutic Uses of Cromolyn Sodium and Nedocromil Sodium?1. Treatment of mild to moderate bronchial asthma to prevent asthmatic attacks. 2. Inhibit both immediate and late asthmatic responses to antigenic challenge or to exercise. 3. With regular use, evidence of reduced bronchial hyperreactivity.Which agents reduce the synthesis of all leukotrienes by inhibiting 5-lipoxygenase enzyme?Leukotriene Inhibitors -ZileutonWhich agents act through antagonism of leukotriene activity at specific receptor sites in the airway, reducing inflammation?Leukotriene Receptor Antagonists -Zafirlukast, MontelukastThese agents are proven effective as prophylactic treatment for mild asthma?Leukotriene Inhibitors -Improvement in lung function and a decrease in symptoms and asthma exacerbation.Which group of drugs inhibit smooth muscle contraction, they are the so called "quick relief medications" for acute relief of asthma?Reliever Drugs 1. Beta-agonists 2. Methylxanthines 3. AnticholinergicsThese medications prevent and/or reverse inflammation for long-term asthma control and prevent exacerbations?Controller Drugs 1. Glucocorticoids 2. Leukotriene Inhibitors and Receptor Antagonists 3. Mast-Cell Stabilizing AgentsThese are episodes of progressive increase in shortness of breath, cough, wheezing, or chest tightness, or some combination of these symptoms?Exacerbation of Asthma or Asthma AttackHow are Exacerbations of Asthma characterized?1. Decrease in expiratory airflow that can be quantified by measurement of lung function (PEF or FEV1). 2. These measurements are more reliable indicators of the severity of airflow limitation than is the degree of symptoms. 3. Degree of symptoms may be a more sensitive measure of the onset of an exacerbation because the increase in symptoms usually precedes the deterioration in peak flow rate.What are the aims of treatment for Exacerbations?1. Relieve Airflow Obstruction 2. Relieve Hypoxemia 3. Plan the Prevention of Future RelapsesWhat are the Primary Therapies for Exacerbations?1. Repetitive administration of Rapid-Acting Inhaled Bronchodilators. 2. Early introduction of Systemic Glucocorticosteroids. 3. Oxygen Supplementation.For patients with Severe Exacerbations, how should they be treated?Acute Care FacilityHow would you define a Mild Exacerbation?1. Reduction in peak flow of less than 20%. 2. Nocturnal Awakenings. 3. Increased use of Short Acting Beta-2 Agonists 4. Can be treated in Community Setting.For a child <5, describe the symptoms of a Mild Exacerbation?Altered Consciousness: No Oximetry: >95% Speech: Sentences Pulse Rate: <100 beats/min Central Cyanosis: Absent Wheeze Intensity: VariableFor a child <5, describe the symptoms of a Severe Exacerbation?Altered Consciousness: Agitated, Confused, Drowsy Oximetry: <92% Speech: Words Pulse Rate: >200 beats/min (0-3 years old) Pulse Rate: >180 beats/min (4-5 years old) Central Cyanosis: Likely Present Wheeze Intensity: Chest may be QuietPhysical activity is a common cause of asthma symptoms, but patients shouldn't avoid exercise. What drugs can prevent the symptoms that appear from physical activity?1. Rapid Acting Inhaled B2-Agonists 2. Leukotriene Modifier or CromonePatients with Moderate to Severe Asthma are advised to receive this vaccine every year?Influenza VaccinationCASE 3CASE 3This is the inflammation of lung tissue?PneumoniaThis is ranked third in the ten leading causes of morbidity in 2000?PneumoniaDescribe the Epidemiology of Pneumonia?1. There are 158 million episodes per year. 2. Cause 3 million deaths or 29% of deaths among children < 5 years old. 3. Incidence is 10-fold higher and number of deaths is 2000-fold higher in developing countries.This condition results from the proliferation of microbial pathogens at the alveolar level and the host's response to these pathogens?PneumoniaWhat are the most common methods by which microorganisms gain access to the lower respiratory tract?1. Aspiration from the Oropharynx -Small volume aspiration during sleep (elderly) and with decreased levels of consciousness. -Many inhaled as contaminated droplets.What are the Mechanical Factors critically important in Host Defense?1. Hairs and Turbinates of Nares catch larger inhaled particles before they reach lower respiratory tract. 2. Branching architecture of the tracheobronchial tree traps particles on the airway lining where mucociliary clearance and local antibacterial factors clear or kill pathogen.What mechanisms offer Critical Protection from Aspiration?1. Gag Reflex 2. Cough MechanismWhen the microorganisms are small enough to be inhaled to the alveolar level, what are extremely efficient at clearing and killing the pathogens?Resident Alveolar MacrophagesWhat assists the Macrophages in clearing and killing the pathogens?Surfactant Proteins A and D that have opsonizing properties or antibacterial or antiviral activity.Once pathogens are engulfed by the macrophages, if they are not eliminated by the macrophage what can kill them?Mucociliary Elevator of the LymphaticsWhat Initiates the Inflammatory Response to support Lower Respiratory Tract Infection?Alveolar MacrophagesWhat Triggers the Clinical Syndrome of Pneumonia?Host Inflammatory ResponseThe release of these substances results in Fever?Interleukin 1 and Tumor Necrosis FactorWhat substances stimulate the release of neutrophils and their attraction to the lung producing both peripheral leukocytosis and increased purulent secretions?IL-8 and Granulocyte Colony Stimulating FactorRelease of these creates Alveolar Capillary Leak, which is initially localized in Pneumonia?Inflammatory MediatorsWhat does Capillary Leak Result in?1. Radiographic Infiltrates 2. Rales detectable on auscultation 3. Hypoxemia which results from Alveolar FillingDecreased compliance due to capillary leak, hypoxemia, increased respiratory drive, increased secretions, and occasionally infection related bronchospasm can lead to this?DyspneaThis results from the spread of infection along the airways, accompanied by direct injury of the respiratory epithelium resulting in airway obstruction from swelling, abnormal secretions, and cellular debris?Viral PneumoniaThis often occurs when respiratory tract organisms colonize the Trachea and gain access to the lungs?Bacterial Pneumonia -Pneumonia may also result from direct seeding of lung tissue after bacteremia.This may evoke an exudative consolidation of pulmonary tissue and involves primarily the interstitium or the alveoli?Bacterial Invasion of Lung ParenchymaThis condition involves the entire lobe and is more common in Community Acquired Pneumonia?Lobar PneumoniaWhat condition is restricted to the alveoli contiguous to the bronchi and are more common in Nosocomial Pneumonia?BronchopneumoniaWhat are the Pathologic Changes that occurs with Pneumonia?Initial Phase: Edema -Proteinaceous exudate and bacteria in the alveoli. -Rarely evident. Red Hepatization Phase -Presence of erythrocytes in cellular intraalveolar exudate. -Neutrophils present for host defense. -Bacteria seen. Gray Hepatization Phase -Erythrocytes lysed and degraded. -Neutrophil is predominant cell. -Fibrin deposition abundant. -Bacteria disappeared. -Corresponds with successful containment of the infection and improvement in gas exchange. Resolution -Macrophage is dominant cell. -Debris of neutrophils, bacteria, and fibrin cleared. -Inflammatory response cleared. *Best described for Pneumococcal Pneumonia (S. pneumoniae).This organism produces a local edema that aids in the proliferation of organisms and their spread into adjacent portions of the lung, often resulting in focal lobar involvement?S. pneumoniaeThis organism attaches to the respiratory epithelium, inhibits ciliary action and leads to cellular destruction and inflammatory response in the submucosa?M. pneumoniae *As infection progresses, sloughed cellular debris, inflammatory cells, and mucus cause airway obstruction, with spread of infection along the bronchial tree.This is an infection of the lower respiratory tract in more diffuse infection with interstitial pneumonia?Group A Streptococcus Infection *Necrosis of tracheobronchial mucosa, formation of large amounts of exudate, edema, and local hemorrhage, with extension into the interalveolar septa, and involvement of lymphatic vessels and increased likelihood of pleural involvement.This manifests in confluent Bronchopneumonia, which is often unilateral and characterized by presence of extensive areas of hemorrhagic necrosis and irregular areas of cavitation of the lung parenchyma resulting in pneumatoceles, empyema, or bronchopulmonary fistulas?S. aureus pneumoniaDespite radiographic appearance, Viral and Pneumocystis Pneumonias represent these types of process?AlveolarWhat are the Noninfectious causes of Pneumonia?1. Aspiration of Food or Gastric Acid 2. Foreign Bodies 3. Hydrocarbons and Lipoid Substances 4. Hypersensitivity Reactions 5. Drug or Radiation Induced PneumonitisWhat is the most common bacterial pathogen in children 3 weeks to 4 years old?Streptococcus pneumonia (Pneumococcus)What are the most frequent pathogens in children 5 years and older?1. Mycoplasma pneumonia 2. Chlamydia pneumoniaWhat pathogens are the major cause of hospitalization and death from bacterial pneumonia among children in developing countries?1. S. pneumonia 2. H. influenzae 3. S. aureusWhat is a prominent cause of lower respiratory tract infections in infants and children < 5 years old?Viral PathogensAt what age is the highest frequency of viral pneumonia occurring?2-3 years oldWhat are the major pathogens in children < 3 years old?1. H. influenzae 2. Respiratory Syncytial VirusWhat is the most frequent pathogen for neonates, < 3 weeks old?1. Group B StreptococcusWhat are is the most frequent pathogen for children aged 3 weeks - 3 months?Respiratory Syncytial VirusWhat is the most frequent pathogen for children aged 4 months to 4 years old?Respiratory Syncytial VirusWhat is the most frequent pathogen for children > 5 years old?M. pneumoniaFor patients who are 3 weeks - 3 months old and are afebrile, what pathogen do you consider?Chlamydia trachomatisDescribe the Morphology of Group B Streptococcus (or STreptococcus agalactiae)?1. Gram (+) cocci in chains, Catalase (-). 2. Facultative anaerobe and Beta Hemolytic. 3. Large mucoid colonies. 4. Hydrolyze sodium hippurate and (+) CAMP test.What is the Morphology of Chlamydia pneumonia?1. Small gram (-) bacteria. 2. No peptidoglycan layer and no muramic acid. 3. Obligate intracellular parasite. 4. Both DNA and RNA. 5. Elementary Body: Confers stability. 6. Reticulate Body: Active form that divides and synthesizes RNA, DNA, and proteins.What is the Morphology of Mycoplasma pneumonia?1. Small coccoidal to short branched filamentous. 2. Bulbous Enlargement with a differentiated tip stricture (most distinctive feature). 3. Lack a peptidoglycan cell wall. 4. Medium must be rich in cholesterol and nucleic acids (purines and pyrimidines). 5. "Fried Egg" appearance of colonies.What is the Morphology of Legionella Pneumophila?1. Rod-shaped organism with flagella. 2. Visualized by Dieterle Silver Impregnation Stain and Direct FA. 3. Charcoal Yeast Extract Agar for medium. 4. Requires cysteine for growth. 5. Hydrolyzes starch, gelatin, and hippurate.These type of pneumonia are often preceded by several days of symptoms of an URTI, typically rhinitis and cough?Viral and Bacterial PneumoniasFor this type of pneumonia, the fever is usually lower than bacterial pneumonia?ViralWhat is the most consistent clinical manifestation of pneumonia?TachypneaSevere infection of pneumonia can be accompanied by these symptoms?Cyanosis and Respiratory FatigueWhat are Clinical Manifestations of Pneumonia?1. Increased work breathing accompanied by intercostal, subcostal, and suprasternal retractions. 2. Nasal flaring. 3. Use of accessory muscles of breathing. 4. Circumoral Cyanosis may be observed.For a patient with pneumonia, what can auscultation of the chest reveal?1. Crackles. 2. Wheezing (difficult to localize in children with hyperresonant chests).In adults and older children this type of pneumonia begins suddenly with a shaking chill followed by a high fever, cough, and chest pain?Bacterial PneumoniaIn older children and adolescents, a brief upper respiratory tract illness is followed by abrupt onset of shaking chill and high fever accompanied by drowsiness with intermittent periods of restlessness, rapid respirations, dry, hacking, unproductive cough, anxiety, and occasionally delirium in this pneumonia?Bacterial PneumoniaWhat do many children with pneumonia do to minimize pleuritic pain and improve ventilation?1. Splinting on affected side. 2. Lie on their side with their knees drawn up to their chest.Early in the course of Pneumonia, what may the physical findings be?1. Diminished breath sounds. 2. Scattered crackles. 3. Rhonchi over affected lung field.Physical Exam of a patient with pneumonia may vary with these complications?1. Pulmonary Consolidation or Complications 2. Pleural Effusion 3. Empyema 4. Pyopneumothorax *Dullness on percussion noted. *Diminished breath sounds. *Lag in respiratory excursion on affected side.Abdominal pain is common in this type of pneumonia?Lower Lobe PneumoniaWhat are the clinical manifestations of pneumonia in infants?1. Prodrome of URTI. 2. Diminished appetite 3. Abrupt onset of Fever 4. Restlessness 5. Apprehension 6. Respiratory DistressHow is respiratory distress manifested in infants?1. Grunting 2. Nasal Flaring 3. Tractions of the supraclavicular, intercostal, and subcostal areas 4. Tachypnea 5. Tachycardia 6. Air Hunger 7. CyanosisInfants with this type of pneumonia may have associated GI disturbances characterized by vomiting, diarrhea, anorexia, and abdominal distention secondary to paralytic ileus?Bacterial PneumoniaIn adults with community acquired pneumonia what are the symptoms commonly seen?1. Febrile 2. Tachycardic 3. Chills or Sweats 4. Cough 5. Pleura involved; Pleuritic Chest Pain 6. GI symptoms 20% of the timeWhat can cause variations in the PE of a patient with pneumonia?1. Pulmonary Consolidation 2. Presence of Absence of Pleural EffusionOn palpation of a patient with pneumonia, what are the findings?Increased or decreased tactile fremitus.On percussion of a patient with pneumonia, what are the findings?Dull to flat, reflecting underlying consolidated lung or pleural fluid.On auscultation of a patient with pneumonia, what are the findings?Crackles, bronchial breath sounds, and possible pleural friction rub.What confirms the diagnosis of pneumonia?Infiltrate on Chest X-RayWhat can an Infiltrate on a Chest X-ray Indicate?Diagnosis of Pneumonia Complication such as pleural effusion or empyemaWhat are the findings of Viral Pneumonia on a Chest Radiograph?Hyperinflation with bilateral interstitial infiltrates and peribronchial cuffing.What are the findings of Pneumococcal pneumonia on a Chest Radiograph?Confluent Lobar ConsolidationWhat is difficult to distinguish from Pneumococcal pneumonia?Atypical pneumonia due to C. pneumonia and M. pneumoniae.In Viral Pneumonia what is the usual WBC count?< 5000 *Predominance of lymphocytesIn Bacterial Pneumonia what is the usual WBC count?15,000 - 40,000 *Predominance of segmentersWhat is the definitive diagnosis of a viral infection?Isolation of a virus or detection of a viral genome or antigen in respiratory tract secretions. *Growth requires 5-10 days. *Shell Viral Cultures need 2-3 days.Acute infection caused by M. pneumonia can be diagnosed based on what tests?1. Positive PCR 2. Seroconversion in an IgG AssayFor mildly ill child with pneumonia, what is the treatment of choice?AmoxicillinIn communities with a high percentage of penicillin resistant pneumococci, what is treat treatment of choice for pneumonia?Amoxicillin *Alternative = Cefuroxime Axetil *Alternative = Amoxicillin/ClavulanateFor School Aged Children with infection of M. pneumonia or C. pneumonia what is the suggested treatment?Macrolide such as AzithromycinIn adolescents with pneumonia what is the treatment suggested?Respiratory Fluoroquinolone (Levofloxacin, Moxifloxacin, Gemifloxacin).What is the mainstay therapy for empiric treatment of suspected bacterial pneumonia in a hospitalized child?1. Parenteral Cefotaxime 2. Ceftriaxone *Approach based on clinical manifestations at time of presentation.If the clinical features suggest Staphylococcal pneumonia (pneumatoceles, empyema) what should initial antimicrobial therapy include?1. Vancomycin 2. ClindamycinIn developing countries what substances helps accelerate the recovery from severe pneumonia?Oral Zinc, 20 mg/dayWhat are the Pulmonary Complications associated with Community Acquired Pneumonia?1. Pleural Effusions or Empyema 2. Pneumothorax 3. Lung Abscess 4. Bronchopleural Fistula 5. Necrotizing Pneumonia 6. Acute Respiratory FailureWhat are the Metastatic Complications associated with Community Acquired Pneumonia?1. Meningitis 2. CNS Abscess 3. Pericarditis 4. Endocarditis 5. Osteomyelitis 6. Septic ArthritisWhat are the Systemic Complications assocaited with Community Acquired Pneumonia?1. Systemic Inflammatory Response Syndrome 2. Sepsis 3. Hemolytic Uremic SyndromeWhat are the Recommendations for Prevention of Pneumonia?1. Children immunized with vaccines for S. pneumonia, H. influenzae, and pertussis. 2. Children >6 months and all adolescents immunized annually for influenza virus. 3. Parents of infants < 6 months, including pregnant adolescents, immunized for influenza virus and pertussis. 4. For High Risk Infants, provide immune prophylaxis with RSV-specific monoclonal antibody.CASE 4CASE 4This is the coughing up of blood/expectoration of blood?Hemoptysis *Bleeding can occur from disruption of the pulmonary or bronchial blood vessels.What are Conditions that present with Hemoptysis?1. Infection 2. Tracheostomy 3. Bronchiectasis 4. Foreign Body 5. Congenital Heart Disease 6. Pulmonary Arteriovenous Malformation 7. Airway Trauma / Lung Contusion 8. Alveolar Hemorrhage Syndrome 9. Pulmonary Thromboembolism 10. Elevated Pulmonary Venous Pressure 11. Tumor/Neoplasms 12. Pulmonary Endometriosis 13. Systemic CoagulopathyDescribe Massive Hemoptysis?1. Coughing up of 300 mL or more per episode of blood. 2. Coughing up >600mL/24 hours. 3. Expectorating an unquantified amount of blood with hemodynamic instability. 4. Coughing up blood with anemia requiring blood transfusion.Describe Non-Massive Hemoptysis?Blood-tinged expectorate, <300mL/episode.Describe the characteristics of Hemoptysis?Appearance: Bright red, mixed with frothy sputum. pH: Alkaline Microscopy: Alveolar macrophage laden with hemosiderin. Manifestations: CoughDescribe the characteristics of Hematemesis?Appearance: Dark red or brownish, contains food particles. pH: Acidic Microscopic: Hemolyzed RBCs. Manifestations: NauseaWhat percentage of the world is infected by M. tuberculosis?1/3What is the infectious agent that kills more youth and adults than any other in the world?M. TuberculosisWhat is the most powerful factor known to increase the risk of progression from TB infection to disease?HIVHow is Tuberculosis spread?Through the airWhat is the main source of infection of Tuberculosis?A person with Pulmonary TB who coughs, sneezes or spits and spreads infectious droplets containing the bacteria in the air.What percentage of people infected with M. tuberculosis develop the active disease?10%What increases the chance of Tuberculosis disease from developing?1. Various physical or emotional stresses. 2. Weakening of the immune system by malnutrition or HIV infection.Left untreated, a person with active TB will infect on average how many people per year?10-15What is the Pathognomonic sign of TB?NONEWhat are the Local Symptoms that present with PTB?1. Cough of two or more weeks. 2. Hemoptysis or recurrent blood-streaked sputum (25% of patients). 3. Chest or back pain not referable to a musculoskeletal disorder. 4. Shortness of breath; dyspnea.What are the Constitutional Symptoms that present with PTB?1. Fever and Chill; intermittent. 2. Progressive Weight Loss 3. Tiredness 4. Night SweatsWhat should be noted in the past history of a patient suggestive of PTB?1. Past history of TB and previous treatment. 2. Vaccination to BCG and previous PPD results. 3. Diseases that increase risk for TB.When is a patient Bacteriologically Confirmed to have TB?Biological Specimen is positive by smear microscopy, culture, or rapid diagnostic tests (Xpert MTB/RIF).When is a patient Clinically Diagnosed to have PTB?Patient has been diagnosed with active TB by a clinician and decided to give the patient a full course of TB treatment. Includes cases diagnosed based on chest x-ray abnormalities or suggestive histology, ane extra-pulmonary cases without laboratory confirmation. *Does not fulfill criteria for bacteriological confirmation.Describe the classification of Pulmonary TB?Cases involving the lung parenchyma.Describe the classification of Extra-Pulmonary TB?A case involving other organs other than the lung including larynx, pleura, lymph nodes, abdomen, genitourinary tract, skin, joints and bones, and meninges. *Laryngeal TB considered extrapulmonary case in absence of lung infiltrates on CXR.What does it mean if it is Smear-Positive?A patient with at least 1 sputum specimen positive for AFB, with or without radiographic abnormalities consistent with active TB.What does it mean if it is Culture-Positive?A patient with positive sputum culture for MTB complex, with or without radiographic abnormalities consistent with active TB.What are the Standards for Diagnosis of TB?Standards 1-6What is Standard 1?Be aware of individual and group risk factors for TB and perform prompt clinical evaluations and diagnostic testing for persons with s/s consistent with TB.What is Standard 2?Patients with unexplained cough lasting 2 or more weeks or with unexplained findings of TB on CXR should be evaluated for TB.What is Standard 3?Patients suspected of PTB should have at least two sputum specimens submitted for smear microscopy.What is Standard 4?Patients suspected of EPTB, appropriate specimens should be collected for examination.What is Standard 5?Patients suspected of PTB with negative sputum smears should have Xpert MTB/RIF or cultures done. *If negative sputum smear, but clinical evidence of TB begin anti-TB treatment after collection of specimens for culture.What is Standard 6?For children suspected of intrathoracic (pulmonary, pleural, and mediastinal or hilar lymph node) TB, bacteriologic confirmation through examination of respiratory secretions.Patients at risk for drug resistance or have HIV risks, or seriously ill, should have what as the initial diagnostic test?Xpert MTB/RIFWhat is the preferred initial microbiological test for suspected tuberculous meningitis?Xpert MTB/RIFWhat diagnostic tests should not be used for diagnosis of active TB?Blood-based serologic tests and interferon-gamma release assays.What are the Standards for treatment of TB?Standards 7-13What is Standard 7?Provider must prescribe an appropriate treatment regimen.What is Standard 8?Give first-line treatment regimen if patient has not been treated previously and does not have risk factors for drug resistance.What is Standard 9?Patient-centered approach to treatment developed.What is Standard 10?Monitor response to treatment of patient with PTB.What is Standard 11?Assessment of the likelihood of drug resistance through drug susceptibility testing.What is Standard 12?Specialized regimen for therapy if suspected drug-resistant organism.What is Standard 13?Record of all medications, tests, and outcomes should be taken.What drug should be omitted in children who are HIV-negative and who have non-cavitary TB?EthambutolDescribe Category I treatment for PTB?2HRZE / 4 HRDescribe Category I treatment for a EPTB case, not involving the CNS or bones and joints?2 HRZE / 4 HRDescribe the Category Ia treatment for EPTB involving the CNS or bones and joints?2 HRZE / 10 HRDescribe the Category II treatment for relapsing PTB or EPTB (no CNS/bones and joints)?2 HRZES / 1 HRZE / 5 HREDEscribe the Category IIa Treatment for relapsing EPTB involving the CNS/bones and joints?2 HRZES / 1 HRZE / 9 HREWhat is the standard regimen for drug-resistant TB such as Rifampicin-resistant TB or Multidrug-resistant TB?ZKmLfxPtoCs -Pyrazinamide -Kanamycin -Levofloxacin -Prothionamide -Cycloserine *At least 18 monthsBased on the weight of the patient how many tablets should be given during the treatment phase?30-37 kg: 2 Tablets 38-54 kg: 3 tablets 55-70 kg: 4 tablets >70 kg: 5 tabletsWhen monitoring the response to a treatment, a patient on category I regimen should be followed up on what months?Month 2 (If negative) - Month 5 + 6 (If positive) - Month 3, then 5 + 6When monitoring the response to a treatment, a patient on category II regimen should follow up on what months?Month 3 + 5 + 8CASE 5CASE 5How many children become ill with TB each year?Half a millionWhat percent of children have TB in their lungs; PTB?70-80%What percent of children have TB in other parts of the body; EPTB?20%What is the gold standard diagnosis for childhood TB?NONEWhat is a common misconception that present a barrier for early recognition and intervention or preventive treatment of childhood TB?Children rarely develop life-threatening TBWhat is referred to as the missing diagnosis because the occurrence of asymptomatic infection?Child TBChildren present with these protean manifestations that are difficult to distinguish from other childhood diseases?1. Fever 2. Cough 3. Weight Loss 4. WeaknessHow does TB usually present in adults compared to children?More localized with pulmonary symptoms like cough and less constitutional manifestations.Children with TB are at a greater risk for what than adults?1. Dissemination 2. Serious Complications 3. DeathWhy is definitive diagnosis by sputum smear and culture of M. tuberculosis more difficult in children?Poor bacteriologic yield brought on by the paucibacillary character of TB in the young and difficult in collecting the specimen.What can provide a presumptive diagnosis in the absence of a positive culture?Demonstration of acid-fast bacilli on microscopy and/or histologic changes on biopsy.What is the first-entry point for the recognition and case finding of TB in children?When there is a symptomatic child consulting for signs and symptoms suggestive of TB and need further studies to confirm the diagnosis.What Is the second-entry point for recognition and case finding of TB in children?Screening of children who belong to the household or close environment of a registered TB case.What is considered TB Exposure?Child is in close contact with a contagious adult or adolescent TB case, but without any signs and symptoms of TB, with negative TST, and no radiologic and laboratory findings suggestive of TB.What is considered TB Infection or Latent TB Infection?A condition in which child has no signs and symptoms presumptive of TB nor radiologic or laboratory evidence, but has a positive TST reaction.What is considered Active TB Disease?A presumptive TB who after clinical and diagnostic evaluation is confirmed to have TB.TB in children usually follows this?Primary TB InfectionTB in adults usually represents this?Reactivation of Previous Infected FociCompare the various clinical features in Pediatric TB?TB Pathogenic Stage: Primary TB Main Diagnostic Confirmation: Clinical features, exposures to active TB case, (+) TST, serial chest x-ray, and DSSM. Bacillary Load: Low, low infectiousness Treatment: 3-4 drugs DOT Mandatory: Yes by parent or health worker.Compare the various clinical features in Adult TB?TB Pathogenic Stage: Secondary (Re-Infection) TB. Main Diagnostic Confirmation: Bacteriology (AFB smear or culture). Bacillary Load: High load (especially in cavitary disease), highly infectious. Treatment: 4-5 drugs. DOT Mandatory: Yes health worker.What is Administrative Order No. 2008-001?Guidelines for Implementing Tuberculosis Control Program in ChildrenWho are Contacts for Screening?Children from 0-4 years old and symptomatic children from 5-14 years old who are in close contact with a case of PTB.A child shall be considered TB symptomatic if at least 3 of these symptoms are present?1. Chronic cough or wheeze >2 weeks. 2. Unexplained fever > 2 weeks (rules out malaria and pneumonia). 3. Unexplained weight loss, failure to gain weight, or loss of appetite. 4. Failure to respond to antibiotics > 2 weeks.What does the diagnosis of Latent TB Infection require?Requires that active TB be excluded from history and PE. *CXR or Bacteriologic Evidence needed before treatment.This is an important tool for TB control and prevention and one of the five criteria in making a presumptive diagnosis of TB?TSTWhat condition in the young is considered a sentinel event, reflecting recent transmission?LTBIWhat is the standard and recommended method of using tuberculoprotein or tuberculin for TB screening?Mantoux Test *Injected intradermally.For who is the Mantoux Test contraindicated in?Persons with severe reaction to a previous TST such as necrosis, blistering, anaphylactic shock, or ulcerationsDescribe the Administration Process of Mantoux Test?1. Locate site on injection, 2 inches below the elbow joint in the volar aspect of the forearm. 2. Clean with alcohol swab and air dry. Use gauge 25 to 27 short bevel needle. 3. Aspirate 0.1 mL of either the 2TU of PPD-RTR 23 or the 5TU of PPD-S and inject needle bevel up intradermally.What is evident after injection of the PPD?Pale Wheal of 6-10 mm in diameter.Some sensitive individuals to the Mantoux Test may develop this?Vesicular or Ulcerating Local Reactions *Less common are regional adenopathy or fever.When should the TST be read?Between 48-72 hoursUp to how long can a positive TST be measured?7 daysUp to how long can a negative TST be measured?72 HoursDescribe an Induration?Palpable, Raised Hardened AreaWhat does an accurate interpretation of the TST require?1. Knowledge of the antigen used (tuberculin). 2. Proper technique for administration and reading. 3. Results of epidemiological and clinical experience. 4. Conditions that can bring about a false positive or negative interpretation.What are the causes of a False-Positive Reaction to TST?1. Infection with nontuberculous mycobacteria. 2. Previous BCG vaccination. 3. Incorrect method of TST administration. 4. Incorrect measurement and interpretation of reaction. 5. Incorrect strength of antigen used.What happens to most patients who receive BCG vaccination during infancy or childhood?Lose their hypersensitivity reaction to tuberculin within 5 years.What are the Factors Related to the Person Being Tested that may cause a False Negative TST Reaction?1. Infections 2. Live attenuated virus vaccinations 3. Metabolic derangements 4. Nutritional factors 5. Diseases affecting lymphoid organs 6. Corticosteroids 7. Age 8. Incubating M. tuberculosisWhat are the Factors Related to the Tuberculin Used that may cause a False Negative TST Reaction?1. Improper storage (exposure to light and heat). 2. Improper dilution 3. Chemical denaturation 4. Contamination 5. Adsorption into the syringeWhat are the Factors Related to the Method of Administration that may cause a False Negative TST Reaction?1. Injection of too little antigen 2. Delayed administration after drawing into syringe 3. Too deep injectionWhat are the Factors Related to Error in Reading and Recording of Results that may cause a False Negative TST reaction?1. Inexperienced reader 2. Conscious or unconscious bias 3. Error in recordingWhat may cause suppression of the tuberculin reaction?Live-virus vaccines against poliomyelitis, varicella, measles, mumps, rubella, rotavirus, or typhoid. *TST postponed at least 4-6 weeks *Can be injected at same time at different anatomical sites.How long should the TST be delayed after a bout of measles, mumps, chicken pox, or whooping cough?2 monthsIn cases of generalized skin lesions such as scabies, impetigo, atopic dermatitis, and allergies how long should TST be delayed?Until lesions have completely healedWhat is incorporated with the diluent for PPD to reduce Adsorption?Tween 80How is contamination avoided when performing TST?Observe Aspetic TechniqueAt what temperature should the tuberculin solution be stored?2-8 degrees CelsiusHow does the WHO define a positive TST?Skin Induration of 10 or > regardless of BCG status.When is an induration of >5 considered positive?1. Severely malnourished children (marasmus or kwashiorkor). 2. Immunocompromised (congenital immune deficiency, HIV/AIDS, or history or immunosuppressants). 3. Contact with infectious TB source. 4. CXR consistent with prior untreated TB. 5. Organ transplant recipients. 6. Taking >15mg/day of prednisone for 1 month or taking TNF-alpha antagonists.What is the inability to react to a TST because of a weakened immune system?AnergyWhat may cause Anergy?1. HIV infection 2. Severe Febrile Illness 3. Measles 4. Hodgkin's Disease 5. Sarcoidosis 6. Live-virus vaccination 7. Corticosteroids or Immunosuppressants 8. Underdeveloped Immune SystemThis refers to a change from a negative to a positive result?Skin Test Conversion *Increase in reaction size to >10 induration within a period of 2 years for a person with previous negative reaction.What is the only vaccine used against TB?Bacille Calmette Guerin (BCG) *Induces artificial primary immunity to TB for prevention of subsequent illness.What is the most widely used vaccine worldwide?BCG *4 billion peopleBCG vaccination of newborns and infants reduces the risk of TB by how much?50% on averageBCG is more effective in preventing the hematogenous spread of tuberculosis bacteria as in these?Meningitis and Miliary FormsWhy should BCG be given at birth?Theory that exposure to mycobacteria can give rise to a cell-mediated response that opposes the protective effect of subsequent BCG vaccination.Why is BCG not recommended in countries where TB rates are low?It increases tuberculin reactivity, making the tuberculin test less accurate.What is the best strategy to eliminate TB?New and more Effective TB vaccineWhat is the best strategy to effectively control TB?Early detection and completion of appropriate treatment of LTBI and TB disease.What are the most favored research strategies currently being developed to prevent TB?1. Recombinant modified BCG vaccines. 2. Attenuated strains of M. tuberculosis. 3. Subunit vaccines. 4. DNA vaccines.What has contributed to the decrease in effectiveness of BCG vaccine?1. Consequence of increased immune suppression by BCG antioxidants. 2. Loss of BCG strain T-cell epitopes as the BCG strain underwent repeated human manipulation over the years.What is the Fixed Dose Combination for TB treatment?Intensive Phase: H = 50mg, R = 75mg, Z = 150mg Continuation Phase: H= 50, R= 75Describe the dosing table for Fixed Dose Combination Treatment for Children?4-7 kg: 1 tablet 8-11 kg: 2 tablets 12-15 kg: 3 tablets 16-24 kg: 4 tablets 25+ kg: Adult Dosages RecommendedWhat drug should be added in the intensive phase for children with extensive disease or living in the setting where the prevalence of HIV or Isoniazid resistance is high?EthambutolFor the patient exposed to Mycobacterium tuberculosis without evidence of infection or active disease what is the objective?Prevent the onset of infection - Primary ProphylaxisFor the patient with latent TB infection what is the treatment objective?Preventing progression of infection to active disease - Secondary ProphylaxisFor a patient classified as having the disease what is the treatment objective?Not only to cure the individual, but to decrease transmission to the community.When should Isoniazid and Rifampicin be taken?On an empty stomach -1 hour before a meal -2 hours after a mealCASE 6CASE 6What are the Standards for Addressing HIV Infection and other Comorbid Conditions?Standards 14-17What is Standard 14?HIV testing and counseling conducted for all patients suspected of having TB.What is Standard 15?For patients with HIV infection and TB, proper treatment should be given.What is Standard 16?Persons with HIV who do not have active TB should be treated for presumed latent TB with isoniazid for 6 months.What is Standard 17?Assessment for comorbid conditions and other factors that could affect TB treatment.In persons with HIV infection and TB with profound immunosuppression (CD4 count less than 50 cells/mm^3) when should ART be initiated?Within 2 weeks of beginning treatment for TB unless TB meningitis is present.For all patients with HIV and TB, regardless of CD4 counts, when should antiretroviral therapy be initiated?Within 8 weeks of beginning TB treatment.Patients with TB and HIV infection should also receive this drug as prophylaxis for other infections?CotrimoxazoleWhat conditions are known to affect the treatment outcome of TB?1. Diabetes Mellitus 2. Drug and Alcohol Abuse 3. Undernutrition 4. Tobacco SmokingWhat are the Standards for Public Health and Prevention?Standard 18-21What is Standard 18?Ensure persons in close contact with patients who have infectious TB be evaluated and managed.What is Standard 19?Children <5 and persons of any age with HIV infection are who in close contact of a person with infectious TB, who after evaluation does not have active TB be treated with isoniazid for 6 months.What is Standard 20?Health care facilities should develop and implement an appropriate TB infection control plan.What is Standard 21?Providers must report both new and retreatment TB cases and their treatment outcomes to local public health authorities.Who are the highest priority contacts for evaluation of TB?1. PErsons with symptoms suggestive of TB. 2. Children < 5 years old. 3. Contacts with known or suspected immunocompromised states, particularly HIV infection. 4. Contacts of patients with MDR/XDR TB.Infection with what increases the likelihood of progression from infection with M. tuberculosis to active tuberculosis?HIVThe absence of these four symptoms in a person living with HIV are unlikely to have active TB?1. Current Cough 2. Night Sweats 3. Fever 4. Weight LossWhat is the initial diagnostic test in adults presumed HIV-associated TB?Xpert(R) MTB / RIFWhat should be done for a patient with presumptive HIV-TB?Referred to nearest DOTS facility or Xpert(R) MTB/RIF facility for more screening and testing before initiating any TB treatment.If Xpert(R) MTB / RIF is negative, what will diagnosis of PTB be based on?High Index of Clinical SuspicionEven in the absence of pulmonary symptoms or signs, the initial evaluation of a patient presumed to have HIV-related TB should always include this?Chest X-RayChest Radiography is an imperfect screen for this TB?Sputum Culture-Positive TB, particularly in patients with advanced immunodeficiency.Upper Lobe Pulmonary Involvement is less frequent in HIV seropositive patients or HIV seronegative patients?HIV Seropositive Patients because of their immunodeficiency.When is Smear-Negative, Culture-Positive TB more common?In patients with Advanced ImmunosupressionThe rate of smear positivity correlates with this?Extent of Radiographic DiseaseWhat is the prophylaxis given for patients with PTB among PLHIV, to prevent Pneumocystis jiroveci pneumonia?Cotrimoxazole Prophylaxis 800 mg Sulfamethoxazole + 160 mg TrimethoprimWhat is the preferred treatment strategy of TB in PLHIV?1. Same as general population. 2. Rifamycin should be given during full course. 3. Efavirenz 600 mg, with 2 NRTIs, along with Rifampin-based TB treatment is preferred strategy.Continuing Cotrimoxazole above CD4 counts of 350 reduced this?1. Hospitalizations 2. Malaria 3. Pneumonia 4. DiarrheaWhen should ART be initiated in PLHIV with TB?After the 2nd week of TB treatment regardless of CD4 count.When should ART be initiated in PLHIV with TB meningitis?After the Intensive Phase of TB treatment.What is the preferred NNRTI for HIV patients on TB treatment?EfavirenzWhat should be avoided for HIV patients on TB treatment?NevirapineHow does Rifampicin reduce the drug levels of both Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI) and protease inhibitors?Through induction of the cytochrome p450 liver enzyme system.Should routine screening for TB be done among patients with Diabetes?Screening for TB in people with DM considered due to high TB prevalence in the Philippines (weak recommendation, low to moderate quality evidence).WHat is one of the risk factors that may increase the risk of progression of latent TB to active TB?Diabetes MellitusWhat subsets of Diabetic patients are at increased risk for TB?1. Type 1 Diabetics 2. Type 2 Diabetics on Insulin Therapy or with Poor Glycemic Control 3. Those with Exposure to Household Contacts with TB 4. Those who SmokeWhat is the treatment regimen for TB among patients with Diabetes?1. Same as general population. 2.For patients with DM who might have TB, when are they at an increased risk for relapse?Patients who have cavitation on initial chest radiograph and who have positive culture at completion of 2 months of therapy. *Continuation phase prolonged to 7 months, making a total treatment period of 9 months.What is used to measure the level of glucose control?HbA1c < 7 FBS < 100 mg/dL ( 70-130 mg/dL)Which drug accelerates the metabolism of sulfonylureas and biguanides which lowers their plasma levels leading to hyperglycemia?RifampicinWhat drug Antagonizes Sulphonylureas causing worsening glycemic control?Isoniazid *Also impairs release and action of insulin leading to hyperglycemia.This drug can reduce immunocompetence because of their MOA, and could possibly worsent the outcome of patients with TB?Dipeptidyl Peptidase IV Inhibitors (Gliptins)For patient with acceptable blood sugar control, with nephropathy or any risk for hypoglycemia, when should insulin be given?Under Physician DescretionWhen can a patient shift from insulin therapy to oral hypoglycemic agents?When the patient is sputum or culture negative and if blood glucose levels are acceptable.What kind of transplant candidates will need dose adjustment based on drug and disease severity?Kidney and Liver Transplant CandidatesFor Post-SOT recipients without risk factor for drug resistance, what is the anti-TB treatment recommended?Intensive Phase: HEZ first 2 months Continuation Phase: HE for 12-18 monthsFor Post-SOT recipients with more severe cases of TB, what is the anti-TB treatment recommended?Intensive Phase: HEZ + R first 2 months Continuation Phase: HR for 4-9 monthsWhat is the most common mode of infection of Tuberculosis?ReactivationWhat are other less common modes of infection of TB?Infected Transplanted Organs and Nosocomial TransmissionWhat are risk factors for post-transplant TB?1. Presence of Chronic Liver Disease 2. Deep Mycoses 3. Pneumocystis jiroveci and Nocardia 4. OKT3 5. CMV 6. Diabetes Mellitus 7. Immunosuppressive Therapy w/ OKT3 and anti-T cell antibodies 8. History of exposure to M. tuberculosis 9. Recipient donor with (+) PPD 10. Radiologic evidence of untreated TBWhat percent of TB occurs in the first year of transplantation?45-60%What is the median time for onset of post transplantation TB?9 months *26 months if received Azathioprine and prednisolone. *11 months if received cyclosporine w/ immunosuppressive agent.A Spanish Group of experts recommended exclusion of this drug for the treatment of post SOT recipients with uncomplicated TB based on the drug's increased risk for hepatotoxicity?RifampicinA Brazilian Group of experts identified the use of this drug as an independent risk factor for liver toxicity?Rifampicin at 600 mgRifampicin and its interaction with immunosuppressive agents increase the chance of this?Graft RejectionThis drug is added for disseminated TB or for transplant recipients with more severe cases?RifampicinFor post SOT recipients with diseases involving the CNS and skeletal system what recommendation was made for treatment?Longer DurationFor CKD, no change in dosing is needed for these drugs because they are excreted via biliary excretion?Isoniazid and RifampicinIf a patient with kidney disease is receiving Isoniazid, what else should be given to prevent peripheral neuropathy?Pyridoxine 10-25 mgWhat drugs are excreted through the kidneys in significant amounts and need dose adjustments for treatment?Ethambutol and Pyrazinamide *3x a weekPatients taking this drug may develop hyperuricemia as a result of inhibition of renal tubular secretion?Pyrazinamide *Periodic monitoring of serum uric acid levels recommended.This drug can cause optic neuritis that results in impairment of visual acuity and color vision and eventually blindness?Ethambutol *Periodic ophthalmologic evaluation recommendedWhat treatment regimen is recommended for advanced CKD (GFR < 30 mL/min)?Single Formulation Anti-TB drugsWhen is the best time to administer anti-TB therapy for a patient undergoing hemodialysis?Immediately after hemodialysis session. *avoids premature removal of drugsWhen is the best time to administer anti-TB therapy for a patient undergoing peritoneal dialysis?AnytimeWhat is the treatment regimen for patients with compensated liver cirrhosis?2HRSE / 6HR 2HSE / 10 HE 2HSE / 9HREWhat is the treatment regimen for patients with decompensated liver cirrhosis?Referral to specialized centers because of possible use of second line TB drugs.Which first line drugs are hepatotoxic?Pyrazinamide (Highest Hepatotoxicity) Rifampin Isoniazid (Lowest Hepatotoxicity) *Can lead to worsening liver function with decompensation of stable cirrhosis and sometimes cause fulminant hepatic failure, with high mortality.What are the safer Anti-TB drugs for Chronic Liver Disease?1. Ethambutol 2. Quinolones 3. Aminoglycosides 4. CycloserineDescribe the available treatment for Childs A, B, and C Cirrhosis?Childs A: Can be given two hepatotoxic drugs in treating compensated cirrhosis. Childs B: One or two hepatotoxic drugs can be given for moderately severe disease. Childs C: Hepatotoxic drugs avoided in decompensated cirrhosis.What treatment regimen is given to patients with liver cirrhosis with encephalopathy and with decompensated liver cirrhosis?Second Line Anti-TB DrugsWhat drug is contraindicated in pregnant women with TB?StreptomycinWhat drug is supplemented in the therapy for pregnant women to prevent peripheral neuropathy?Pyridoxine 10-25 mg/dayPregnant and breastfeeding women are at increased risk of this condition, which is associated with isoniazid?Peripheral NeuropathyIf a patient develops polyneuritis, what should the patient be treated with?Pyridoxine 100-200 mg/dayWomen on first-line regimen are encouraged to breastfeed under what conditions?If they have been treated appropriately for 2 weeks or more and are no longer infectious.For pregnant patients suspected to have MDR TB, treatment should be individualized based on what?1. Drug sensitivity tests 2. Clinical assessment 3. AOG 4. Drug effects on developing fetus *Start with non-injectable regimen and continue until delivery when an injectable agent can be added. *Delay treatment until second trimester.What are the areas of concern of pregnant women to exposure to chest radiography?1. Teratogenicity or birth defects 2. Cancer 3. Germline mutation in exposed fetusWhat is the accepted cumulative dose of ionizing radiation below which clinically manifest effects?<5 radsPotential for increased risk of teratogenicity or birth defects affecting the CNS is observed at what ioning radiation?>50 rads *During 10-17 weeks gestation. *Less risk at 18-27 weeks gestation or before 10 weeks.What is the estimated fetal dose per chest x-ray examination?0.00007 rads *Need >71,000 examinations to reach 5 rads.What is the estimated fetal exposure from CXR (2 views)?0.02 - 0.07 mradWho should be screened and treated for Latent TB Infection among High Risk Clinical Groups?1. PLHIV 2. Solid Organ and Hematopoietic Stem Cell Transplant Recipients 3. Rheumatoid Arthritis on Biologicals 4. Chronic Dialysis 5. Type 1 DM 6. Type 2 DM on insulin therapy with poor glycemic control 7. Diabetics exposed to active TB 8. Diabetics who Smoke 9. Pregnant Women with Exposure to TB 10. Injection Drug Users 11. Pregnant Women with HIVWho is more susceptible to TB, type 1 or type 2 Diabetes Mellitus?Type 1 *Higher among patients using insulin. *Correlation with Glycosylated HemoglobinLatent TB Screening is not routinely recommended for these patients?Pregnant WomenWhat are the Obstetric Complications reported in Pregnant Women with TB?1. Higher rate of spontaneous abortion 2. Small for date uterus 3. Suboptimal weight gain 4. Preterm labor 5. Low birth weight 6. Increased neonatal mortalityWhat is the preferred screening test for LTBI in resource-limited settings, such as the Philippines?Tuberculin Skin Test (TST)What is the Recommended Treatment for LTBI?Isoniazid 300 mg for 6 months under supervised treatment. Pyridoxine at 25 mg/day for prevention of peripheral neuropathy.What can potentiate the risk of peripheral neuropathy seen with Isoniazid?Antiretroviral Therapy such as Dideoxynucleotide (didanosine, stavudine).What are Contraindications of IPT?1. Active Hepatitis (Acute or Chronic) 2. REgular and Heavy Alcohol Consumption 3. Symptoms of Peripheral NeuropathyINH when used with what drugs does not increase risk of hepatitis, the most important adverse reaction?Efavirenz or NevirapineCASE 2CASE 2This is a chronic inflammatory disease of the airways that is associated with widespread, but variable airflow obstruction that is often reversible either spontaneously or with treatment?AsthmaWhat is the Clinical Hallmark of Asthma?Airway Hyperresponisiveness -Presents as widespread narrowing of the airway which results from a variety of stimuli and also intermittent episodes of a constellation symptom in between asymptomatic intervalsWhat is the Pathophysiological Hallmark of Asthma?Reduction in Airway Diameter -Brought by the contraction of smooth muscle or bronchospasm, edema of bronchial wall, mucous plugging, and infiltration of inflammatory cells and desquamation of epithelial and inflammatory cells. -Results in increase in airway resistance, decrease in forced expiratory volumes and flow rates, increase in work of breathing, abnormal distribution of both ventilation and pulmonary blood flow with mismatched ratios.What are the Structural Changes in Asthmatic Airways?1. Subepithelial Fibrosis 2. Airway Smooth Muscle IncreaseWhat causes Subepithelial Fibrosis?1. Deposition of collagen fibers and proteoglycans under the basement membrane, seen in all asthmatic patients. 2. Occurs in other layers of the airway wall, with deposition of collagen and proteoglycans.What causes Increased Airway Smooth muscle?1. Hypertrophy (increased size of cells) 2. Hyperplasia (increased cell division) 3. Contributes to increased thickness of the airway wall. 4. Relates to disease severity and caused by inflammatory mediators such as growth factors.What is the predominant mechanism of airway narrowing?Airway Smooth Muscle Contraction -In response to multiple bronchoconstrictor mediators and neurotransmitters. -Largely reversed by bronchodilators.What causes Airway Edema?1. Increased microvascular leakage in response to inflammatory mediators. 2. May be important in acute exacerbations.What causes Airway Thickening?1. Structural changes termed "remodeling." 2. Important in more severe disease and not fully reversible.What causes Muscle Hypersecretion?1. Due to increased mucus secretion and inflammatory exudates. 2. Leads to luminal occlusion (Mucus Plugging).What are AsthmaRelated Chemical Mediators?1. Histamine 2. Leukotrienes 3. C4, D4, and E4 4. Platelet Activating Factor -Initiate bronchoconstriction, mucosal edema, and early and late immune responses.What are the Histologic Changes seen in Asthma patients?1. Presence of smooth muscle hyperplasia of bronchial and bronchiolar walls. 2. Markedly thickened basement membrane. 3. Variable degrees of mucosal edema. 4. Denudation of bronchial and bronchiolar epithelium. 5. Eosinophilia of the submucosa and secretions is prominent whether or not allergic mechanisms are present.What is the Etiology of Asthma?Combination of environmental exposures and inherent biological and genetic vulnerabilities.Describe the Epidemiology of Asthma?1. One of the most chronic diseases globally affecting 300 million persons. 2. Incidence ranges from 1-18%. 3. Annual worldwide deaths of 250,000. 4. Prevalence in Philippines = 6.2%. 5. Peak Age of Incidence = 3 years old. 6. When young, more males incidents, but equalizes in adulthood. 7. Rising prevalence in developing countries due to urbanization. 8. Reduced in children raised in a rural setting (linked to endotoxin in these environments).What are the Host Factors that can increase risk for Asthma?1. Genetic 2. Obesity 3. SexWhat are the Environmental Factors that can increase risk for Asthma?1. Allergens 2. Infections (Viral) 3. Occupational Sensitizers 4. Tobacco Smoke 5. Outdoor/Indoor Air Pollution 6. DietWhat are the four major areas focused on for the search of genes linked to the development of asthma?1. Production of allergen-specific IgE antibodies (atopy). 2. Expression of airway hyperresponsiveness. 3. Generation of inflammatory mediators such as cytokines, chemokines, and growth factors. 4. Determination of the ratio between Th1 and Th2 immune responses.The gene governing airway hyperresponsiveness is located where?Near a major locus that regulates serum IgE levels on chromosome 5q.What are the genes that are associated with the response to asthma treatments?1. Variations in gene encoding beta-adrenoceptor linked to differences in subjects' responses to beta2-agonists. 2. Other genes of interest modify responsiveness to glucocorticosteroids and leukotriene modifiers.What mediator may affect airway function and increase likelihood of asthma development and is related to obesity?LeptinsWhat are risk factors associated with Sex for asthma?Children: 2x higher in males: <14 years of age. Adult: Higher in Women. -Lung size is smaller in males than in females at birth but larger in adulthood: may contribute to change incidence.What is the role of Allergens in increasing the risk for Asthma?1. Sensitization to house dust mite allergens, cat danger, dog danger, and Aspergillus mold are independent risk factors for asthma-like symptoms in children up to 3 years of age.What has shown to be an important cause of allergic sensitization, particularly in innercity homes?Cockroach InfestationThese two conditions produce a pattern of symptoms including bronchiolitis that parallels many features of childhood asthma?1. Respiratory Syncytial Virus (RSV). 2. Parainfluenza VirusDescribe the Hygiene Hypothesis?Suggests that exposure to infections early in life influences development of child's immune system along a "nonallergic" pathway," leading to a reduced risk of asthma and other allergic diseases. -Measles and sometimes RSV can protect against the development of asthma.What are the Occupational Sensitizers that can increase risk for Asthma?1. Highly reactive small molecules such as isocyanates. 2. Irritants that can cause alteration in airway responsiveness. 3. Known immunogens such as platinum salts. 4. Complex plant and animal biological products that stimulate production of IgE.What is the most common occupational respiratory disorder in industrialized countries?AsthmaWhat is the most important method of preventing occupational asthma?Elimination or reduction of exposure to occupational sensitizers.How does Tobacco Smoke increase the risk for Asthma?1. Associated with accelerated decline of lung function in people with asthma, increases in asthma severity may render patients less responsive to treatment.Infants of smoking smothers are how many more times more likely to develop wheezing illnesses in the first year of life?4xExposure to environmental tobacco smoke (passive smoking) increases risk of these?1. Lower Respiratory Illnesses in infancy and childhood.How does diet affect a patient with Asthma?1. Infant fed formulas or intact cow's mild or soy protein gave higher incidence of wheezing. 2. Increased processed food and decreased antioxidant, increased n-6 polyunsaturated fatty acid (fruits and vegetables) and decreased n-3 polyunsaturated fatty acid (oily fish).What are the most common chronic symptoms of asthma?1. Intermittent Dry Cough 2. Expiratory WheezingOlder children and adults will report these associated symptoms?1. Shortness of Breath 2. Chest TightnessYounger children are more likely to develop this associated symptom?Intermittent, Nonfocal Chest PainWhat are other Asthma symptoms seen?1. Respiratory symptoms worse at night. 2. Difficulty in filling their lungs with air. 3. Increased ventilation and use of accessory muscles. 4. General fatigue, maybe due to night disturbances.What are the typical Physical Signs of Asthma?1. Expiratory Wheezing (some Inspiratory) 2. Rhonchi 3. Hyperinflation 4. In children, predominant Nonproductive CoughDescribe the uses of Spirometry in testing for Asthma?1. Assess degree of airway obstruction. 2. Assessing response to treatment. 3. Evaluating the long-term course of the disease. 4. FVC, FEV1, MMEF (FEF), and PEFR all measured, showing reduced values.Describe the uses of Peak Flow Meter in testing for Asthma1. Measure PEFR when spirometer is not available. 2. PEFR correlates with FEV1. 3. Fall in PEFR predicts onset of asthma exacerbation. Males = (height in cm - 100) 5 + 175 Females = (height in cm - 100) 5 + 170What is the MOA of B-Adrenergic Receptor Agonists?Anti-asthmatic action is due to direct relaxation of airway smooth muscle producing bronchodilation.What are the two ways bronchodilation is produced in BAdrenergic Receptor Agonists?1. Stimulation of B2-adrenergic receptor in bronchial smooth muscle leads to activation of adenylyl cyclase which increases cellular cyclic AMP leading to a reduction of smooth muscle tone. 2. B2-adrenergic receptor agonists increase conductance of K channels in airway smooth muscles leading to membrane hyperpolarization and relaxation.What are the other effects of B2 Adrenergic Receptor Agonists?1. Suppress the release of leukotrienes and histamine from mast cells in lung tissue. 2. Enhance mucociliary function. 3. Decrease microvascular permeability. 4. Inhibits phospholipase A2.What are examples of Short-Acting BAdrenergic Receptor Agonists?1. Salbutamol or Albuterol 2. TerbutalineDescribe ShortActing BAdrenergic Receptor Agonists?1. For acute inhalation or oral treatment of bronchospasm, "reliever drugs." 2. Onset of action of 1-5 minutes lasting 2-6 hours. 3. Topical application through aerosols, which produce high local concentrations in the lungs with low systemic delivery, improving therapeutic ratio by minimizing systemic side effects.Describe Terbutaline?1. Maximum plasma concentration within 3 hours. 2. First metabolism in intestinal wall and liver. 3. Bioavailability = 10%. 4. Metabolized by conjugation with sulfuric acid and excreted as sulfate conjugate.Describe Albuterol?1. Inhaled, 10-20% reaches lower airways. 2. Remainder is retained in delivery system or deposited in oropharynx where it's swallowed. 3. Fraction deposited in airways is absorbed into pulmonary tissues and circulation. 4. In systemic circulation it becomes accessible to hepatic metabolism and excreted in urine as unchanged drug and as phenolic sulphate (inactive metabolite).Describe LongActing BAdrenergic Receptor Agonists such as Salmeterol?1. Bronchodilation for over 12 hours. 2. Extended side chain make it more lipophilic than albuterol. 3. Lipophilicity regulates the diffusion rate away from the receptor by determining the degree of partitioning in lipid bilayer of the membrane.What are the Adverse Effects of B-Adrenergic Receptor Agonists?1. Increased Heart Rate 2. Cardiac Arrythmias 3. CNS Effects: Headaches, sleep disturbances, agitation, hyperactivity, and restlessness. 4. Skeletal Muscle Tremors 5. Muscle Cramps 6. Metabolic Disorders: Increased glucose, lactate, and free fatty acids in plasma - In DM, hyperglycemia may worsen. 7. Hypersensitivity Reactions: Angioedema, urticaria, bronchospasm, hypotension, and collapse.What is the use of Steroids in treatment of Asthma?Potent and broad antiinflammatory efficacy.What are the routes of administration of steroids?1. Parenteral and Oral Corticosteroids most beneficial in acute illness. 2. Inhaled Corticosteroids for long term control.What is the MOA of Steroids?1. Effective in inhibiting airway inflammation due to the following events -- 2. Modulation of cytokine and chemokine production. 3. Inhibition of eicosanoid synthesis. 4. Inhibition of accumulation of basophils, eosinophils, and other leukocyte in the lung tissue. 5. Decreased vascular permeability.What drug is used for treatment of transplant rejection and autoimmune disorders?1. Prednisone 2. Prednisolone 3. Other Glucocorticoids w/ Immunosuppressive AgentsWhat is the MOA of Adrenocortical Steroids?1. Steroids lyse and induce redistribution of lymphocytes, causing rapid, transient decrease in peripheral blood lymphocyte counts. 2. Broad anti inflammatory effects on cellular immunity. 3. Little effect on humoral immunity. 4. Downregulation of proinflammatory cytokines such as IL-1 and IL-6. 5. T cells are inhibited from making IL2. 6. Activation of cytotoxic T cells inhibited. 7. Neutrophils and monocytes display poor chemotaxis and decreased lysosomal enzyme release.This is used to reverse acute transplant rejection and acute exacerbation of selected autoimmune disorders?Intravenous Methylprednisolone Sodium Succinate (SOLU-MEDROL, AMETHAPRED).What are the Therapeutic Uses of Adrenocortical Steroids (Glucocorticoids)?1. Prevent and treat transplant rejection. 2. Treatment of graft-versus-host disease in bone-marrow transplantation. 3. To treat rheumatoid arthritis, SLE, systemic dermatomyositis, psoriasis, asthma, inflammatory bowel disease, inflammatory ophthalmic diseases, autoimmune hematologic disorders, and acute exacerbations of multiple sclerosis. 4. Limit allergic reactions that occur with other immunosuppressive agents that are used in transplant recipients to block first-dose cytokine storm caused by treatment with muromonab-CD3.What are the Toxic effects of Adrenocortical Steroids?1. Growth Retardation 2. Avascular Necrosis of Bone 3. Osteopenia 4. Increased Risk of Infection 5. Poor Wound Healing 6. Cataracts 7. Hyperglycemia 8. HypertensionThe concomitant therapy of glucocorticoids plus this has allowed a reduction in the dosages of steroids administered?CyclosporineWhat are the most common effects with systemic corticosteroid treatment that lasts for only 5-10 days?1. Mood Disturbances 2. Increased Appetite 3. Loss of Glucose Control in Diabetes 4. CandidiasisWhich agents inhibit antigeninduced bronchospasm as well as prevent the release of histamine from sensitized mast cells?Mast Cell-Stabilizing AgentsWhat is the MOA of Cromolyn Sodium and Nedocromil Sodium, the Mast-CellStabilizing Agents?1. Inhibiting mediator release from bronchial mast cells. 2. An ability to reverse increased functional activation in leukocytes. 3. Suppression of the activating effects of chemotactic peptides on human neutrophils, eosinophils, and monocytes. 4. Inhibition of parasympathetic and cough reflexes. 5. Inhibition of leukocyte trafficking is asthmatic airways.Describe the Pharmacokinetic Properties of Mast-Cell Stabilizers?1. Only 1% of oral dose is absorbed. 2. Excreted unchanged in urine and bile. 3. Peak concentration within 15 minutes. 4. Half life of 45-100 minutes.What are the Toxic effects of Mast-Cell Stabilizers?1. Bronchospasm 2. Coughing 3. Wheezing 4. Laryngeal Edema 5. Joint Swelling and Pain 6. Angioedema 7. Headache 8. Rash 9. Nausea 10. Bad Taste -Adverse reactions are infrequent and minor. -Ineffective in treating ongoing bronchoconstriction.What are the Therapeutic Uses of Cromolyn Sodium and Nedocromil Sodium?1. Treatment of mild to moderate bronchial asthma to prevent asthmatic attacks. 2. Inhibit both immediate and late asthmatic responses to antigenic challenge or to exercise. 3. With regular use, evidence of reduced bronchial hyperreactivity.Which agents reduce the synthesis of all leukotrienes by inhibiting 5-lipoxygenase enzyme?Leukotriene Inhibitors -ZileutonWhich agents act through antagonism of leukotriene activity at specific receptor sites in the airway, reducing inflammation?Leukotriene Receptor Antagonists -Zafirlukast, MontelukastThese agents are proven effective as prophylactic treatment for mild asthma?Leukotriene Inhibitors -Improvement in lung function and a decrease in symptoms and asthma exacerbation.Which group of drugs inhibit smooth muscle contraction, they are the so called "quick relief medications" for acute relief of asthma?Reliever Drugs 1. Beta-agonists 2. Methylxanthines 3. AnticholinergicsThese medications prevent and/or reverse inflammation for longterm asthma control and prevent exacerbations?Controller Drugs 1. Glucocorticoids 2. Leukotriene Inhibitors and Receptor Antagonists 3. Mast-Cell Stabilizing AgentsThese are episodes of progressive increase in shortness of breath, cough, wheezing, or chest tightness, or some combination of these symptoms?Exacerbation of Asthma or Asthma AttackHow are Exacerbations of Asthma characterized?1. Decrease in expiratory airflow that can be quantified by measurement of lung function (PEF or FEV1). 2. These measurements are more reliable indicators of the severity of airflow limitation than is the degree of symptoms. 3. Degree of symptoms may be a more sensitive measure of the onset of an exacerbation because the increase in symptoms usually precedes the deterioration in peak flow rate.What are the aims of treatment for Exacerbations?1. Relieve Airflow Obstruction 2. Relieve Hypoxemia 3. Plan the Prevention of Future RelapsesWhat are the Primary Therapies for Exacerbations?1. Repetitive administration of Rapid-Acting Inhaled Bronchodilators. 2. Early introduction of Systemic Glucocorticosteroids. 3. Oxygen Supplementation.For patients with Severe Exacerbations, how should they be treated?Acute Care FacilityHow would you define a Mild Exacerbation?1. Reduction in peak flow of less than 20%. 2. Nocturnal Awakenings. 3. Increased use of Short Acting Beta-2 Agonists 4. Can be treated in Community Setting.For a child <5, describe the symptoms of a Mild Exacerbation?Altered Consciousness: No Oximetry: >95% Speech: Sentences Pulse Rate: <100 beats/min Central Cyanosis: Absent Wheeze Intensity: VariableFor a child <5, describe the symptoms of a Severe Exacerbation?Altered Consciousness: Agitated, Confused, Drowsy Oximetry: <92% Speech: Words Pulse Rate: >200 beats/min (0-3 years old) Pulse Rate: >180 beats/min (4-5 years old) Central Cyanosis: Likely Present Wheeze Intensity: Chest may be QuietPhysical activity is a common cause of asthma symptoms, but patients shouldn't avoid exercise. What drugs can prevent the symptoms that appear from physical activity?1. Rapid Acting Inhaled B2- Agonists 2. Leukotriene Modifier or CromonePatients with Moderate to Severe Asthma are advised to receive this vaccine every year?Influenza Vaccination
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