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82 title slides 246 total slides Lecture 47-49 – not included We are nearly finished with our first year! Congratulations everyone! 1 1. 2. 3. 4. Define asthma Workup for possible asthma Associations and triggers for asthma Treatment categories of asthma 2 EXAM … Kudlak’s said “know these” Symptoms/definition of asthma Variable obstruction Testing CXR, PFT (spirometry), methacholine challenge Presentation FamHx, allergies, eczema 2 tables Intermittent Mild Treatment algorithm 3 1. Define asthma 4 Asthma VARIABLE Airflow Obstruction - Disease of the airways Reversibility Inflammation Infiltration of inflammatory cells and mediators Mucous gland hyperplasia and production Remodeling … if untreated Basement membrane thickening, smooth muscle hyperplasia and transition to squamous epithelium 5 Symptoms and Complaints Dyspnea at rest or exertion Cough Wheezing What is a wheeze? Symptom, non specific Wheezing vs stridor ○ Wheeze – expiratory Stridor – inspiratory (e.g. vocal cord dysfunction, granulation [d/t poor previous ET intubation]) 6 2. Workup for possible asthma 7 Ancillary Studies CXR - PA & lateral Spirometry – pre & post bronchodilator Methacholine Challenge HRCT Cardiopulmonary Exercise Testing IgE & RAST Exhaled NO - eNO 8 CXR & HRCT CXR May be normal Abnormal findings: ○ Hyperexpansion ○ Mucous plugging and atelectasis HRCT may reveal: Air Trapping Mucous plugging and atelectasis Remodeling 9 Spirometry (PFT) FEV-1/FVC – is obstruction present or not? FEV-1 / FVC < 70% = obstruction present FEV-1 – severity of obstruction 70% = mild 50% = severe 30% = very severe FEF 25-75 – thought by some to reflect the small airways. 10 Methacholine Challenge Bronchoprovacation – methacholine, mannitol, histamine i.e. provoking an asthma attack Serial measurement of FEV-1 at increasing concentrations of methacholine Provocative Concentration of methacholine to produce a 20% decrease in FEV-1 PC02- at 8 mg/ml Can demonstrate hyperresponsiveness and reversibility Discontinuation of medications prior to testing. 11 3. Associations and triggers for asthma 12 Common Link/Associations Triggers Family History Allergy – Atopy (IgE) Eczema AR = allergic rhinitis PND = paroxysmal nocturnal dyspnea GERD … MedHx of every single S.P. this block Seasonal allergies – AR, PND GERD Changes in temperature and or humidity Cats Dust Mites Mold Upper respiratory infections First and second hand smoking Fragrances 13 4. Treatment categories of asthma 14 Treatment Goals Reduce symptoms and limitations Identify triggers Prevent remodeling Objectively measure control of disease Education: Maintenance - long term care (change the car’s oil) Rescue – short term fix ○ Intermittent, mild asthma (albuterol, 2 days in spring and 2 days in fall) Use of MDI 15 16 Categories of asthma: Intermittent vs. mild/persistent Intermittent i.e. high school football player wheezes 2x/year (fall and spring) Nocturnal awakenings (< 2 times / month) # uses of rescue inhaler (< 2 days / week) Mild (persistent) Nocturnal awakenings (> 3 times / month) # uses of rescue inhaler (> 2 days / week) Severe Symptoms all day long 17 18 Treating asthma: Intermittment vs. mild/persistent Refer to figure on previous slide, steps 1-3 (SABA ICS ICS + LABA) Intermittent asthma SABA PRN (albuterol) Mild, persistent asthma Low dose ICS (fluticasone) Persistent asthma (using ICS and SABA 4x/day) ICS + LABA (Advair, Symbicort, Breeu) 19 Abbreviations/Tx options SABA LABA ICS 20 SABA … Short Acting Beta Agonist Quick acting, short lasting Rescue therapy for symptom relief Increased use usually indicates a need for step up in therapy Relaxes bronchial smooth muscles They do not control the underlying inflammation Beta – 2 agonists Most common are albuterol and levalbuterol 21 LABA … Long Acting Beta Agonist i.e. symbicort, advair All have a black box warning Smart Trial lessons learned Never use LABA to Tx asthma without an inhaled corticosteroid Patients die if you change from SABA LABA (without adding ICS) Proper changes: SABA ICS ICS + LABA Can decrease need for repetitive SABA use Effective in decreasing night time symptoms Can be given by MDI or Nebulized 22 ICS (Inhaled Corticosteroids) i.e. fluticasone Treat the underlying inflammation The most effective maintenance medication Reduce the number and activity of inflammatory cells in the airways Minimal absorption into the systemic circulation Excellent deposition in target tissue Can be given by MDI or Nebulized 23 1. 2. 3. 4. 5. Micro of acute bronchitis URI viruses Treatment for acute exacerbations Workup and treatment Flu treatments 24 1. Micro of acute bronchitis 25 Acute Bronchitis Generally cause by a virus Influenza A and B Para influenza Coronavirus Rhinovirus RSV (Respiratory syncytial virus) Human metapneumovirus 26 Acute Bronchitis Other Pathogens: Mycoplasma pneumoniae - pharyngitis, constitutional symptoms and cough. (Common case) Chamydophilia pneumoniae - pharyngitis, laryngitis and bronchitis, hoarseness and low grade fever.( 5% of cases) Pertussis - 1% of cases in US 27 2. URI viruses 28 URI Epidemiology Seasonal Patterns: Rhinoviruses and Para influenza Fall and late spring Non-seasonal Patterns: Adenoviruses Military facilities, daycare centers and hospital wards RSV and coronaviruses Winter and spring Enteroviruses Summer 29 URI Virology Over 200 subtypes of viruses Rhinovirus which includes more than 100 serotypes is the most common (30-50%) Coronaviruses responsible for 10-15% Influenza virus responsible for 5-15% Respiratory syncytial virus (RSV) responsible for 5% Most are capable of reinfection 30 3. Treatment for acute COPD exacerbations 31 COPD treatment Oxygen How much? IV solumedrol (60-125mg) vs PO prednisone (30-60mg) ○ 2 Liters ○ IV – if pt cannot breathe well or swallow Is hypercapnia a problem? ○ PO – at home therapy ○ Yes, watch out for acidosis and low mental status ○ Non-rebreather can worsen hypercapnia Bronchodilators beta adrenergic agents - albuterol anticholinergic agents ipratropium Steroids – reduce inflammation Antibiotics? YES BiPAP vs. intubation? If looking crappy but can follow commands, consider BiPAP If unable to follow commands, ET intubation 32 4. Workup and treatment 33 4a. Workup 34 A 56 year old male with a PMHx of COPD presents with a c/c of increasing cough and sputum production. What questions should you ask? Fever? Constitutional? Eating? Sleeping? Able to get out of bed? CXR? Yes, especially if (1) COPDers are looking worse than normal, OR (2) O2 sat is unresponsive to O2 therapy Labs? ABG? Determine pt baseline (PaO2 and PaCO2) Is patient part of 50/50 club? PaO2 = 50, PaCO2 = 50 Antibiotics? Yes, especially for COPDers getting worse Admission? If they look bad (SEE NEXT SLIDE) 35 COPD admission … these make sense Inadequate response to treatment – no change Marked increase in dyspnea – more dyspnea Inability to eat or sleep due to symptoms – anorexia, insomnia Worsening hypoxemia (drop from PaO290 82) Worsening hypercapnia – PaCO2 (50-70) Changes in mental status Inability to care for oneself High risk comorbidities including pneumonia, cardiac arrhythmia, CHF, DM, renal failure or liver failure Uncertain diagnosis 36 4b. Treatment 37 COPD treatment … same as slide 32 Oxygen How much? IV solumedrol (60-125mg) vs PO prednisone (30-60mg) ○ 2 Liters ○ IV – if pt cannot breathe well or swallow Is hypercapnia a problem? ○ PO – at home therapy ○ Yes, watch out for acidosis and low mental status ○ Non-rebreather can worsen hypercapnia Bronchodilators beta adrenergic agents - albuterol anticholinergic agents ipratropium Steroids – reduce inflammation Antibiotics? YES BiPAP vs. intubation? If looking crappy but can follow commands, consider BiPAP If unable to follow commands, ET intubation 38 5. Flu treatments 39 Acute Bronchitis Mycoplasma pneumoniae or Chlamydophila pneumoniae Suspect with prolonged cough and URI symptoms Treatment: tetracyclines, macrolides and fluoroquinolones Pertussis Treatment: erythromycin or clarithromycin Influenza Consider treatment of neuraminidase inhibitors if symptoms onset within 48 hours (oseltamivir, zanamavir) Supportive therapy (hydration) 40 1. 2. 3. 4. Define emphysema, chronic bronchitis PFT in COPD Classes of drugs with mechanisms Adult bronchiectasis causes 41 1. Define emphysema, chronic bronchitis 42 1a. Define emphysema 43 Emphysema - Clinical definition Emphysema Chronic progressive dyspnea with little sputum production, hypoxemia, decreased expiratory flow and end stage cachexia. 44 Emphysema - Anatomical definitions Permanent enlargement of the air spaces (acini) distal to the terminal bronchioles. Centrilobular or Centriacinar emphysema. Disease of respiratory bronchioles (primarily) This is a common finding in smokers. Panacinar or Panlobular emphysema Disease of entire air space, acini, distal to the terminal bronchiole This is more common in Alpha-1 anti-trypsin deficiency. Possible for combinations of disease entities 45 1b. Define chronic bronchitis 46 Clinical Definition Chronic Bronchitis Persistent cough resulting in sputum production for more than 3 months in each of the past 2 years . 47 2. PFT in COPD 48 49 Lung Function; Normal and abnormal 1. Most adult nonsmoking men show a decline in their forced expiratory volume in 1 second (FEV1) of 35-40ml/year 2. Smokers show a decrease in the FEV1 of 45-60ml/yr. 3. Those who smoke and develop COPD show loses of FEV1 of 70-120ml/yr.!!!50 Normal Pulmonary Function Test: VOLUMES: TV = Tidal Volume IRV= Inspiratory Reserve Volume ERV = Expiratory Reserve Volume RV= Residual Volume FEV1 = Forced Expiratory Volume in the first second CAPACITIES: TLC = Total Lung Capacity IC = Inspiratory Capacity = TV + IRV FRC = Functional Residual Capacity, ERV + RV VC or FVC= Vital Capacity or Forced Vital Capacity = IRV + TV + ERV. 51 52 3. Classes of drugs with mechanisms 53 Therapy and Prevention: Bronchodilators (SABA, LABA) Beta 2 agonists - open airways Anticholinergic Block secretions Steroids (PO vs. IV vs. ICS) Reduce inflammation Oxygen (acute vs. chronic AND QHS vs. continuous) Increase O2 sat Antibiotics (for acute exacerbations) Limit infections Holistic and Surgical: Smoking cessation Avoid airway irritants Diet Exercise Chest Physical Therapy OMT Chronic Pulmonary Rehabilitation Lung Resection, Bullectomy Mucolytic agents Thin mucus secretions Vaccinations (Pneumococcal and influenza vaccines) Prevention 54 Inhaled bronchodilators Relaxation airway smooth muscle Decreases mast cell mediator release Increases mucociliary clearance Increases mucus secretion (thinned) 55 4. Adult bronchiectasis causes 56 Causes/Etiology of Bronchiectasis 1/3 of cases – unknown etiology (unknown cause) 1/3 of case - infections Pertussis in children MAI (mycobacterium avium) in adults Remaining 1/3 (other): Genetic - Cystic Fibrosis, Primary ciliary dyskinesia, and alpha1-antitrypsin deficiency Anatomic - dysphagia and esophageal dysfunction Immune and autoimmune - Primary Hypogammaglobulinemia, HIV, RA and Sjogren’s 57 Bronchiectasis - definition Abnormal and permanent dilation of the bronchi caused by repeated cycles of infection and inflammation 58 1. 2. 3. 4. 5. Incidence of lung cancer 6. Pancoast definition / associations 7. Horners syndrome 8. CA with keratinization Treatment of squamous CA early Small cell systemic complications, histologic cells Treatment of Small cell early Stage IV treatment 59 1. Incidence of lung cancer 60 Incidence = # new cases / unit time Lung cancer is the most common cancer worldwide, Estimated 1,600,000 new cases and 1,380,000 deaths in 2008. In the United States, there will be an estimated 226,000 new cases of lung cancer and 160,000 deaths in 2012. Around 1953, lung cancer became the most common cause of cancer deaths in men, and in 1985, it became the leading cause of cancer deaths in women. Lung cancer deaths have begun to decline in men, reflecting a decrease in smoking. The rise in the death rate in women appears to have reached a plateau, although almost one-half of all lung cancer deaths now occur in women. The term lung cancer, or bronchogenic carcinoma, refers to malignancies that originate in the airways or pulmonary parenchyma. Approximately 95 percent of all lung cancers are classified as either small cell lung cancer (SCLC) or nonsmall cell lung cancer (NSCLC). This distinction is essential for staging, treatment, and prognosis. Other cell types comprise about 5 percent of malignancies arising in the lung (mesothelioma d/t asbestos exposure)s 61 2. Pancoast definition / associations 62 Pancoast's syndrome Lung cancers arising in the superior sulcus cause a characteristic Pancoast's syndrome manifested by: Pain (usually in the shoulder, and less commonly in the forearm, scapula, and fingers), Horner's (ptosis, miosis, and anhidrosis), Bony destruction, and Atrophy of hand muscles. Pancoast's syndrome is most commonly caused by NSCLC (typically squamous cell) and only rarely by SCLC . 63 64 3. Horners syndrome 65 Horner's syndrome (ipsilateral ptosis, anhidrosis, and miosis) may be due to invasion of the last cervical or first thoracic segment of the sympathetic trunk (T4 disease). 66 Horner’s Syndrome Pancoast's syndrome — Lung cancers arising in the superior sulcus cause a characteristic Pancoast's syndrome manifested by Pain (usually in the shoulder, and less commonly in the forearm, scapula, and fingers), Horner's = ipsilateral ptosis, miosis, and anhidrosis ○ Usually due to pancoast tumor invasion of superior cervical ganglion Bony destruction, and Atrophy of hand muscles. Pancoast's syndrome is most commonly caused by NSCLC (typically squamous cell) and only rarely by SCLC . 67 4. CA with keratinization 68 EXAM!!! SQUAMOUS CELL CARCINOMA (NSCLC) … KERATINIZATION 69 CLINICAL MANIFESTATIONS • Paraneoplastic phenomena (COMLEX) — Paraneoplastic effects of tumor are remote effects that are not related to the direct invasion, obstruction, or metastasis. • Hypercalcemia — Hypercalcemia in patients with lung cancer may arise from a bony metastasis or less commonly tumor secretion of a parathyroid hormone-related protein (PTHrP), calcitriol or other cytokines, including osteoclast activating factors. Cases with hypercalcemia are divided as such: squamous cell carcinoma (51%), adenocarcinoma (22%), and SCLC (15%). Most patients with hypercalcemia have advanced disease (stage III or IV) and a median survival of a few months . • Symptoms of hypercalcemia include anorexia, nausea, vomiting, constipation, lethargy, polyuria, polydipsia, and dehydration. Confusion and coma are late manifestations, as are renal failure and nephrocalcinosis. Symptomatic patients who have serum calcium of 12 or higher require treatment that includes hydration and bisphosphonate. 70 5. Treatment of squamous CA (NSCLC) early 71 NSCLC (Squamous) Treatment • • • Surgical resection offers the best opportunity for longterm survival and cure in patients with resectable NSCLC. The appropriateness of surgical resection of candidates with known or suspected NSCLC includes preoperative staging and an assessment of performance status with concurrent comorbidities and pulmonary function to allow prediction of postoperative function. A patient with lung cancer may be "resectable" by virtue of having a surgically removable NSCLC, but may not be "operable" due to poor pulmonary function or comorbidities. Patients with stage I or II NSCLC should be treated with complete surgical resection whenever possible. • Postoperative adjuvant chemotherapy has been shown to improve survival in patients with pathologic stage II disease and may have a role for patients with stage IB NSCLC. 72 6. Small cell systemic complications, histologic cells 73 6a. Small cell (SCLC) systemic complications 74 CLINICAL MANIFESTATIONS SIADH secretion — The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is frequently caused by SCLC and results in hyponatremia. Symptoms include anorexia, nausea, and vomiting. Cerebral edema can occur with the onset of hyponatremia is rapid. Symptoms caused by cerebral edema may include irritability, restlessness, personality changes, confusion, coma, seizures, and respiratory arrest. Treatment of SIADH focuses on treating the malignancy. In the majority of patients with SCLC, the hyponatremia will resolve within weeks of starting chemotherapy. Neurologic — Lung cancer is the most common cancer associated with paraneoplastic neurologic syndromes; typically these are associated with SCLC. Paraneoplastic neurologic syndromes are thought to be immunemediated, and autoantibodies have been identified in a number of instances. 75 CLINICAL MANIFESTATIONS These diverse neurologic manifestations include, but are not limited to, Lambert-Eaton myasthenic syndrome (LEMS), cerebellar ataxia, sensory neuropathy, limbic encephalitis, encephalomyelitis, autonomic neuropathy, retinopathy, and opsomyoclonus . The most common of these is LEMS, which may be seen in approximately 3 percent of patients with SCLC. The neurologic symptoms of LEMS precede the diagnosis of SCLC in more than 80 percent of cases, often by months to years. Paraneoplastic neurologic syndromes generally do not improve with immunosuppressive treatment. However, symptoms may stabilize with response of the underlying neoplasm to treatment. 76 CLINICAL MANIFESTATIONS • • • Hypertrophic osteoarthropathy — Hypertrophic pulmonary osteoarthropathy (HPO) is defined by the presence of clubbing and periosteal proliferation of the tubular bones associated with lung cancer or other lung disease. Clinically, HPO is characterized by a symmetrical, painful arthropathy that usually involves the ankles, knees, wrists, and elbows. The metacarpal, metatarsal, and phalangeal bones may also be involved. Dermatomyositis and polymyositis — Dermatomyositis and polymyositis are two distinct forms of inflammatory myopathy, both of which are manifested clinically by muscle weakness. These inflammatory myopathies can be the presenting symptom in patients with lung cancer or can develop later in the course of disease. Cushing's syndrome — Ectopic production of adrenal corticotropin (ACTH) can cause Cushing's syndrome. Patients typically present with muscle weakness, weight loss, hypertension, hirsutism, and osteoporosis. Hypokalemic alkalosis and hyperglycemia are usually present. Cushing's syndrome is relatively common in patients with SCLC and with carcinoid tumors of the lung. Patients with Cushing's syndrome and SCLC appear to have a worse prognosis than patients with SCLC without Cushing's syndrome. 77 6b. Small cell histologic cells 78 EXAM!!! SCLC … small blue cells 79 7. Treatment of Small cell (SCLC) early 80 SCLC Treatment Patients with limited stage SCLC • Primary Tx = combination of chemotherapy and radiation therapy, • Addition of radiation therapy has been shown to prolong survival compared to chemotherapy therapy alone. • Surgery is palliative…is not used except in the rare patient who presents with a solitary pulmonary nodule without metastases or regional lymph node involvement. SCLC HAPPENS SO FAST THAT THERE IS USUALLY NO TIME FOR SURGICAL RESECTION. For patients with extensive stage SCLC, • Chemotherapy alone is used as the initial therapy. • Prophylactic radiation has been shown to decrease the incidence of brain metastases and prolong survival in patients with both limited and extensive stage SCLC who respond to their initial treatment. 81 8. Stage IV treatment 82 Treatment (NSCLC) Patients with stage IV disease • Systemic therapy OR • Symptom-based palliative approach. • In appropriately selected patients, chemotherapy and/or molecularly targeted therapy may prolong survival without sacrificing quality of life. • Radiation therapy and surgery may also be useful for symptom palliation in some patients. Patients with stage IV disease based upon the presence of an isolated metastasis (brain, adrenal) • May benefit from resection of the metastasis as well as aggressive treatment of the primary tumor… palliative, NOT curative 83 1. 2. 3. 4. 5. ABG interpretation Define ARDS Inhalation toxins & treatment Sleep apneas (central v. sleep) Treat lung symptoms anaphylaxis 84 1. ABG interpretation Refer back to Dr. J’s CM Lecture 34 (block 4) if this doesn’t make sense 85 ABG Normal Measures: PaO2 (>80 mmHg) PaCO2 (35-45 mmHg) pH (7.35-7.45) SaO2 (>95%) HCO3 (21-27 mEq/L) 86 ABG pH 7.25 PaO2 92 PaCO2 82 Sat 90% HCO3 30 87 2. Define ARDS 88 Acute Respiratory Distress Syndrome (ARDS) Acute, diffuse, inflammatory lung injury that leads to: Increased pulmonary vascular permeability (thick and soggy lungs) Increased lung weight Loss of aerated tissue Hypoxemic respiratory failure Involves both lungs aka Shock lung 89 ARDS Pathological Hallmark is diffuse alveolar damage Alveolar edema with or without focal hemorrhage Acute inflammation of the alveolar walls and hyaline membranes 90 ARDS Clinical features: Rapid onset of 6-72 hours Worsens rapidly Dyspnea, cyanosis (hypoxemia), and diffuse crackles Tachypnea, tachycardia, diaphoresis and use of accessory muscles May also have cough and chest pain 91 ARDS - Testing ABG: Hypoxemia Respiratory alkalosis Elevated alveolar-arterial oxygen gradient (increased A-a gradient) CXR (Chest X-ray): Bilateral alveolar infiltrates 92 3. Inhalation toxins & treatment 93 Inhalation Injuries Simple asphyxiants: Work related during the use of liquefied gas or airline respirators or working in confined spaces Inert Produce toxicity by displacing oxygen and lowering FIO2 Treatment: Removal from exposure, Supplemental oxygen 94 Inhalation injuries Pulmonary irritants: Chlorine, ammonia, sulfur dioxide, phosgene, etc. Dissolve in the respiratory tract mucous and alter the airlung interface by invoking an irritant or inflammatory response. Produce and acid or alkaline product or direct cellular toxicity Treatment: Bronchospasm-nebulizer, Consider early intubation 95 Inhalation injuries Smoke inhalation – fires Heat transfer causing damage and toxins produced by the fire are adsorbed onto carbonaceous particles that deposit in the airways Treatment: Rapid intubation, oxygen, nebulizers. Possible broncholavage to clear debris and toxins from distal airways 96 Inhalation injuries Hydrogen sulfide Petroleum refinery and sewage storage tank workers Rotten egg smell Pulmonary irritant and cellular poison 97 Inhalation injuries Cyanide Many commercial uses Bitter almonds Rapidly absorbed, inhibition of oxidative metabolism Tissue hypoxia in seconds to minutes Coma, seizures, cardiovascular collapse Antidote Sodium thiosulfate 98 Inhalation injuries Carbon monoxide Most common cause of acute poisoning death Prevents binding of O2 to hemoglobin and shifts the oxyhemoglobin dissociation curve to the left interfering with the ability of normal hemoglobin to release its bound O2 to the tissues Coma, seizures, cardiac arrest Treatment O2, hyperbaric 99 4. Sleep apneas (central v. obstructive) 100 4a. Sleep apneas (central) 101 Central sleep apnea (CSA) Repetitive cessation or decrease of both airflow and ventilatory effort during sleep Primary – just happens Secondary - include Cheyne-Stokes breathing, medical condition, a drug/substance abuse Hyperventilation related CSA (brain causes tachypnea) 102 Central sleep apnea Disrupted sleep with excessive daytime sleepiness Poor subjective sleep quality “I am not sleeping well” Insomnia Inattention Poor concentration Morning headaches Nocturnal angina 103 Central sleep apnea Diagnosis - in lab polysomnography 3 findings > 5 central apneas per hour of sleep Excessive daytime sleepiness, awakening with SOB, frequent arousals and awakening during sleep, or insomnia Not explained by another sleep disorder, medical disorder, neurological disorder, medication use or substance abuse 104 4b. Sleep apneas (obstructive) 105 Obstructive sleep apnea (OSA) Definition Obstructive apneas and hypopneas caused by repetitive collapse of the upper airway during sleep (think obesity) 106 Obstructive sleep apnea Clinical presentation Daytime sleepiness (“I am tired”) Loud snoring Gasping, snorting or interruptions in breathing while sleeping 107 Obstructive sleep apnea Diagnostic tests Full-night in-laboratory polysomnography Diagnosis: 15 or more apneas per hour of sleep OR Diagnosis: 5 or more obstructive apneas per hour of sleep in a patient with signs and symptoms of disturbed sleep 108 5. Treat lung symptoms anaphylaxis 109 Anaphylaxis Treatment: Assess for early intubation for airway issues i.e. large uvula Epinephrine!!! IM or IV 2 large bore IV’s Oxygen Volume resuscitation with IV fluids 110 Anaphylaxis Epinephrine doses: IM 0.3 -0.5 mg (1 : 1,000) Infants and children IM 0.01 mg per kg (1 : 1,000) IV infusion preferred over bolus dose 2-10 micrograms per minute (1:10,000) ALWAYS do 1 : 10,000 first = proper dilution If you did 1 : 1,000 first, cause severe HTN CVA and MI No absolute contraindications to the use of epinephrine 111 Anaphylaxis Adjunctive therapies: Always in addition to epinephrine Antihistamines – H1 (Benadryl) or H2 (Zantac …if unresponsive) Bronchodilators - albuterol Glucocorticoids – prevents collapse after stable Other vasopressors 112 There are some good CM Pearls floating around for these 3 lectures. 113 1. 2. 3. 4. 5. Histology of acute TB lymph PPD immune reaction Isolation for TB Immunocompromised workup for TB Ranges for positive PPD 114 Lecture 50-51 Practice Questions 115 Question #1 80 year old nursing home resident presents to the ER with cough. He has no other complaints. Nursing home care giver is present and states four days ago he was well. ER work up is done including bacterial and acid fast testing samples, CXR, and lab work is done. He is eventually diagnosed with bronchitis and sent back to the NH on a Z-pack. You as his primary care are notified the next day that his the acid fast stain is positive. What now? A. Do nothing, await further testing from the laboratory B. Isolate him, use airborne precautions, await further laboratory testing C. Isolate him, order Chest CT scan, and more sputum cultures D. Isolate him, order Chest CT scan, more sputum cultures, and start him on TB treatment 116 Question You are called by the director of your local hospital ER for the evaluation of several people concerned that they may have TB. The people work on different floors of an office building. Yesterday it was reported to them that the night janitor had recently passed away from TB meningitis 3 weeks ago. Several of the people remember passing him in the hallway. The next step in the management of these patients is which of the following? A. Lumbar puncture and place a PPD B. Place a PPD only, if positive in 48-72 hours then proceed to lumbar puncture C. Place a PPD, order a chest X-ray and if either are abnormal then proceed to lumbar puncture D. Give reassurance 117 1. Histology of acute TB lymph 118 Path Necrotizing granuloma or caseating granuloma is composed of palisading of epithelioid histiocytes at the margin of the necrosis; i.e., the nuclei are lined up perpendicular to the necrotic center. On AFB stains, organisms are found mainly in the zone of necrosis. 119 “Red snappers” “Serpentine cording” 120 Primary infection Inhalation of airborne droplet nuclei size is important (1-5 microns in MTB) First 3-4 weeks little immune response develops due to number of interacting factors (low organism #, TB immune system inhibiting factors) During this initial phase, the organism spreads (disseminated TB) via macrophages into the surrounding lymphatic system and via blood to other organs although primary infectious spread to other organs is very rare. If conditions favor an early immune response then a Ghon complex will form and be visible on CXR early on. Later on as the immune system response increases caseating granulomas will form with later granuloma formation in an attempt to either eradicate the disease or reach a stalemate in the form of Latent TB 121 2. PPD immune reaction 122 PPD Mantoux 5 Tuburculin skin test (PPD) Due to a delayed hypersensitivity or type IV reaction Tuberculin skin test conversion … increase of >10mm induration at 2 years Read PPD in 48-72 hours (most positive @ 48hrs) Boosting …. “2 step ppd” ( second step in 3-4 weeks), not well supported, only used in cases of suspected anergy or in patient that get tested frequently (i.e.) medical student 123 PPD Measure wheel from insideout (in mm) Feels like a bumpy orange (raised and erythematous) 124 Neither are positive 125 3. Isolation for TB To me, this could have two meanings: 1. We are supposed to isolate patients with TB 2. How do we isolate the TB pathogen? 126 Question #1 80 year old nursing home resident presents to the ER with cough. He has no other complaints. Nursing home care giver is present and states four days ago he was well. ER work up is done including bacterial and acid fast testing samples, CXR, and lab work is done. He is eventually diagnosed with bronchitis and sent back to the NH on a Z-pack. You as his primary care are notified the next day that his the acid fast stain is positive. What now? A. Do nothing, await further testing from the laboratory B. Isolate him, use airborne precautions, await further laboratory testing C. Isolate him, order Chest CT scan, and more sputum cultures D. Isolate him, order Chest CT scan, more sputum cultures, and start him on TB treatment 127 Culture Remains gold standard for confirming diagnosis of TB Culture all specimens, even if smear or NAA negative Results in 4–14 days when liquid medium systems used Culture monthly until conversion, i.e., 2 consecutive negative cultures 128 Colonies of M. tuberculosis Growing on Media 129 Direct Detection Using Nucleic Acid Amplification (NAA) NAA tests rapidly identify a specimen via DNA and RNA amplification Benefits may include Earlier lab confirmation of TB disease Earlier respiratory isolation and treatment initiation Improved patient outcomes; interruption of transmission Perform at least 1 NAA test on each pulmonary TB suspect A single negative NAA test does not exclude TB 130 Invasive testing Bronchoscopy useful Transbronchial biopsies increase diagnostic yield Gastric contents (am specimen) sometimes in young children Needle bx of pleura with pleural effusion granulomas in up to 60% but culture of pleural fluid on 25% cases positive 131 4. Immunocompromised workup for TB 132 Primary TB infection Composes 2/3 of all MTB infections Immunocompetant host’s pulmonary infections develop primarily in the upper lobes eventually leading to cavitary lesions rich in MTB (105-108 bact) Older and severely immunocompromised hosts Middle to lower lobe disease with or without cavitations Both immunocompromised and immunocompetent * could stop at this stage however, if not then hematogenous spread will occur Miliary TB, is a reference to chest x-rays that have a specific pattern. Observed only in disseminated TB More common to chronic forms of TB 133 “Millet seeds” http://radiopaedia.org/cases/miliary-tuberculosis-2 134 Miliary TB 135 Suspected Co-infection of TB and HIV 2010 Co-infected study NEJM 2010(362)707-16 136 5. Ranges for positive PPD 137 PPD cutoffs based risk stratification - Immunosupressed particularly defects in cellular response www.cdc.gov/ppd 138 Positive PPD/Latent TB evaluation STOP 139 PPD Type of Reaction Possible Cause False-positive Nontuberculous mycobacteria BCG vaccination*** False-negative Anergy Recent TB infection Very young age (< 6 months old) Live-virus vaccination Overwhelming TB disease 140 1. 2. 3. 4. PPD testing Treatment for different PPD results Define MDRTB Side effects of TB drug treatments 141 Other Exam Questions 142 Question 85 year old native SC male presents to your office from home due to a persistent productive cough, low grade fever, and 10 lbs weight loss over the past 2 months. Chest x-ray shows significant bilateral fibrosis with no mass or cavitations. No history of tobacco usage. Further history reveals that he underwent treatment for TB at the age of 6. He otherwise feels fine and would like to get back to sitting for his grandchild. Please choose one of the options below: A. B. C. D. Place a PPD and if positive treat for active TB Place a PPD, perform AFB sputum stain/culture x3 samples, treat if positive Isolate patient, perform AFB sputum stain/culture x 3 samples, treat if positive Isolate patient, perform a bronchoscope and collect samples for stain and culture including AFB, treat if positive 143 Question A. B. C. D. 32 year old Hispanic female school teacher presents to your office for preemployment physical evaluation required by your local school district. Part of the evaluation requires a PPD to be placed. Born in Brazil and left at the age of 8 years old. She was told as a child that any PPD skin testing would be positive as she received the BCG vaccination as a child. She states no TB contacts as a child and has no complaints presently. What is the next best step in the management of this patient? Place the PPD anyway Order a chest x-ray to rule out past or current TB disease Order chest x-ray and three sputum samples at least 24 hours apart You remembered Dr. Cook’s email and quickly send an E-consult 144 Question 55 year homeless female is involved in a hit and run. Past history is significant for TB of which she is currently taking medication for. She is admitted to the hospital and continued on her prior medications. Ten days following ORIF of her left femur you are called to the bedside after she is found to be hypotensive. Basic appropriate testing is done. Hct is 20 and her PT/INR is prolonged. Which of the following is the most likely cause of your patient’s condition? A. B. C. D. Drug to drug interaction Hemophilia Surgical complication Bacterial sepsis 145 Question A ESRD patient is found to have a PPD of 12 mm on routine screening. CXR shows no abnormalities. What is the next best step in the management of this patient? A. Place the patient on latent TB therapy B. Place another PPD in 3-4 weeks, if positive treat for latent TB C. Order a CT chest due to chance plain CXR is wrong, if abnormal treat for latent TB D. Order CT chest and 3 consecutive daily AFB sputum samples, if abnormal treat for latent TB 146 1. PPD testing … repeat?? 147 PPD Mantoux 5 Tuburculin skin test (PPD) Due to a delayed hypersensitivity or type IV reaction Tuberculin skin test conversion … increase of >10mm induration at 2 years Read PPD in 48-72 hours (most positive @ 48hrs) Boosting …. “2 step ppd” ( second step in 3-4 weeks), not well supported, only used in cases of suspected anergy or in patient that get tested frequently (i.e.) medical student 148 PPD cutoffs based risk stratification - Immunosupressed particularly defects in cellular response www.cdc.gov/ppd 149 Positive PPD/Latent TB evaluation STOP 150 PPD Type of Reaction Possible Cause False-positive Nontuberculous mycobacteria BCG vaccination*** False-negative Anergy Recent TB infection Very young age (< 6 months old) Live-virus vaccination Overwhelming TB disease 151 Other methods for detecting Mtb IGRAs: QuantiFERON-TB Gold In-Tube (QFT-GIT)®, and T-Spot.TB® These tests do not exclude LTBI or TB disease Decisions about medical/public health management should include other info/data, and not rely only on TST/IGRA results Should be considered equivalent to PPD 152 2. Treatment for different PPD results 153 Treatment Goal is to eliminate bacilli without resistance Multiple drugs to which organisms are sensitive Add at least 2 new drugs if failure suspected Safest / shortest effective therapy Ensure compliance 154 Latent TB Treatment Below used in non-MDR suspected patients Regimens INH x 9 months (Why not 6 months or 12 months) INH +Rifapentine 12 weekly doses – $$$ INH +RIF 3 months (not used) RIF +PZA x 2 mo ( now discouraged due to excessive hepatotoxicity) RIF x 4 mo 155 Active Pulmonary Tb & HIV – Previously untreated can generally be tx with 6 or 9 month regimens Initial 2 months RIPE = (RIF+INH+PZA+EMB) Additional 4 month drop Strep and pyrazinamide (PZA) = IRE = (INH + RIF + EMB) – (PZA) Pregnant women should not take pyrazinamide 156 Active Pulmonary Tb & + HIV Much more complex. Basic approach similar but Longer duration of treatment Drug interactions with HIV meds ○ Rifamycins and protease inhibitors and non-nucleoside reverse transcriptase inhibitors DOT (directly observed therapy) for all HIV Pyridoxine (vitamin B6) for all HIV 157 Second Line drugs for TB Quinolones esp. moxifloxacin Cycloserine Ethionamide Capreomycin Other aminoglycosides ..amikacin, kanamycin Streptomycin – not used often today (nephrotoxic) Para-aminosalicylic acid – not a good therapy (usually 3rd line drug) 158 3. Define MDRTB 159 Multidrug-Resistant (MDR) and Extensively DrugResistant (XDR) TB MDR TB caused by bacteria resistant to best TB drugs, isoniazid and rifampin XDR TB caused by organisms resistant to isoniazid and rifampin, plus fluoroquinolones and ≥1 of the 3 injectable second-line drugs All TB TB with any drug resistance MDR TB* with drug resistance to at least the firstline drugs isoniazid and rifampin XDR TB** with drug resistance to the first-line drugs isoniazid and rifampin and to specific second-line drugs *Often resistant to additional drugs **Resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin 160 What five patient characteristics might make you suspect drugresistant TB even before you have drug susceptibility test results? Mandell’s Textbook, 7th. Edition, Ch 250 Q1: Where can you get answers to these five questions? Q2: If you either know, or even just suspect, that your patient has TB which is (i) DR, (ii) MDR, (iii) MDR or (iv) TDR…. To whom would you look for advice regarding formulating a regimen which might be able to cure the patient…. And render him non-infectious? Remember that with TB you are NEVER ALONE. Behind you are DHEC and CDC…. And beyond them a whole national network of resources (e.g. the RMTCCs and much more!) 161 How MDR comes about Weak DOT programs Unreliable drug supply Uncontrolled usage of 2nd line drugs Inability of local laboratories to test for drug resistance 162 4. Side effects of TB drug treatments 163 Isoniazid (INH)BQ Inhibits mycolic acid synthesis Main toxicities: Hepatitis Neuropathy (can avoid with vit B6) ○ Rare, occurs 4-5 months out Drug interaction ○ Dilantin metabolism 164 Rifampin (RIF)BQ Inhibits DNA-dependant RNA polymerase “-cidal” Broad spectrum Adverse effects Hepatitis Drug interactions ○ CYP450 inducer (i.e. coumadin / contraceptives) Rash – red man Changes body fluids color and stains everything including contact lenses Flu like illness 165 Rifapentine (RIFP) Highly protein bound rifamycin family drug Allows long half life compared to rifampin Now approved for usage in HIV (-), non-cavitary latent MTB treatment in 12 week regiment with INH SE – same as rifampin 166 Pyrazinamide (PZA) Bacteriostatic …. Inhibits fatty acid synthesis Adverse effects Hepatotoxicity (combined with INH therapy) Not used in combo therapy anymore in USA Unusual arthralgias without arthritis Nausea / vomiting 167 Ethambutol (EMB)BQ Bacteriostatic Inhibit proper attachment of mycolic acids to complex cell wall sugars Adverse effects Optic neuritis (red - green color testing) Hyperuricemia Peripheral neuropathy (rare) Ishihara Test What number is here? 168 Monitoring therapy LFTs (hepatotoxicity) for INH at initiation Visual acuity / red-green (optic neuritis) color testing with EMB Audiometry (ototoxicity) if streptomycin (esp prolonged) Monthly questioning rather than tests for liver disease Sputum at 1 and 2 months ….if still + additional testing for MDRTB and look for non-adherence MDRTB monthly during entire treatment course 169 1. 2. 3. 4. 5. Micro of CAP Viral agents in CAP IV drug user pneumonias Alcoholic pneumonias Predictors of mortality and ICU admissions with CAP 170 Lecture 52-53: Ones I thought could be exam questions 171 EXAM!!! CAP- causative agents – bacterial most common Streptococcus pneumonia Staphylococcus aureus Haemophilus influenzae Mixed anaerobes (aspiration) Enterbacteriaceae Pseudomonas aeruginosa Legionella spp. 172 EXAM!!!! CAP - causative agents - viral - adults - common Influenza A and B RSV Human metapneumovirus Adenovirus types 4 and 7 (in military recruits) 173 EXAM!!! Pneumonia Syndromes Acute CAP – most common CAP in the older adult (>60yo) Nursing home pneumonia CAP in patients with HIV/AIDS Severe CAP Health Care-Associated Pneumonia (HCAP) Atypical pneumonia syndrome Aspiration pneumonia - alcoholics Pulmonary infiltrates with eosinophilia Nosocomial pneumonia and pneumonia in ICH 174 CAP-duration of therapy The classic 10-14 days was unsupported by evidence. Clinical stability occurs more quickly, therefore antibiotic therapy can be discontinued earlier. Mild to moderate severity: 3-7 days Adjunct therapy: corticosteroids, macrolides, statins; all due to antiinflammatory effects; study results have been contradictory and no clear role has been defined 175 HAP/VAP pathogenesis Outcome depends on: Number and types of colonizing pathogens that enter the LRT Host’s mechanical, cellular, and humoral defenses HAP-microaspiration ○ Sedation, vomiting, impaired swallowing, intubation during surgery VAP ○ Leakage around cuff ○ Inhalation of contaminated aerosols ○ Reflux of contaminated ventilator tubing condensate ○ Local trauma and inflammation from the endotracheal tube ○ Biofilm encased bacteria in the ETT lumen 176 Ventilator-associated events (VAE) Based on objective, streamlined, and potentially automatable criteria Three definition tiers Ventilator associated condition (VAC) Infection-related ventilator associated condition (IVAC) Possible and probable VAP 177 VAP-diagnosis New VAE criteria focuses on: Indicators of worsening of oxygenation Fever OR leukocytosis/leukopenia AND A new antimicrobial agent(s) is started and continued for at least 4 days Purulent respiratory secretions/positive cultures 178 HAP/VAP Principles of Antibiotic Therapy Assess risks for MDR pathogens Obtain blood and sputum for smear and culture Begin empirical early, appropriate, and adequate antibiotic regimen Assess clinical response at 24-48 hours, review microbiologic data, de-escalate initial antibiotics if possible Nonresponders vs. responders 179 HAP/VAP Evaluation of clinical nonresponders Wrong diagnosis? Wrong therapy? Wrong pathogen? Complication? Superinfection? 180 CMS “Never Events” Unintended retention of foreign object (surgery) Air embolism (product or device) Death or serious disability due to hemolytic transfusion reaction or hypoglycemia, stage III or IV pressure ulcers (Case Management) Death or serious disability from a fall (Environmental) Infection VAP - possible CLABSI - impossible CAUTI - impossible Clostridium difficile - impossible MRSA - impossible SSI in CABG, Gastroenterotomy, certain ortho procedures, laparoscopic gastric restriction surgery Manifestations of poor glycemic control Deep vein thrombosis/pulmonary embolism in TKA/THA 181 1. Micro of CAP 182 EXAM!!! CAP- causative agents – bacterial most common Streptococcus pneumonia Staphylococcus aureus Haemophilus influenzae Mixed anaerobes (aspiration) Enterbacteriaceae Pseudomonas aeruginosa Legionella spp. 183 2. Viral agents in CAP 184 EXAM!!!! CAP - causative agents - viral - adults - common Influenza A and B RSV Human metapneumovirus Adenovirus types 4 and 7 (in military recruits) 185 3. IV drug user pneumonias 186 CAP - Radiologic Exams Chest x-ray/computed tomography (CT)/nuclear medicine procedures demonstrate CAP: Lobar Nodular Upper lobe vs. lower lobe peribronchial Diffuse bilateral interstitial (upper/lower) Cavitary abscesses Septic emboli – IV drug users Pneumatoceles Pleural effusions (layered out or loculated) 187 4. Alcoholic pneumonias 188 EXAM!!! Pneumonia Syndromes Acute CAP – most common CAP in the older adult (>60yo) Nursing home pneumonia CAP in patients with HIV/AIDS Severe CAP Health Care-Associated Pneumonia (HCAP) Atypical pneumonia syndrome Aspiration pneumonia – alcholics Pulmonary infiltrates with eosinophilia Nosocomial pneumonia and pneumonia in ICH CAP - impairment of pulmonary defenses Altered level of consciousness Cigarette smoke Alcohol Infections may interfere with normal ciliary function, chemotaxis, phagocytosis Iatrogenic manipulations, medications Older age select immunodeficiency, immunosuppressive agents Structural lung abnormalities, COPD, obstruction 190 5. Predictors of mortality and ICU admissions with CAP 191 Severe CAP-Prediction Scores Modified British Thoracic Society severity score The pneumonia Patient Outcome Research Team (PORT) score (aka pneumonia severity index – PSI) Confusion, Urea, Respiratory rate, low Blood pressure (CURB) score (and CURB-65) Confusion Urea > 20 RR > 30 HoTN Age > 65yo Best predictors of mortality and need for ICU 192 1. 2. 3. 4. Micro of VAP/HAP Pathophysiology of HAP/VAP Treatment plans for HAP/VAP (empiric) Antibiotic coverage for VAP/HAP 193 Nosocomial Pneumonia Nosokomos (Greek)- “one who tends the sick”….circa 1843: acquired or occurring in a hospital Hospital Acquired Pneumonia (HAP) Occurs in a patient who has been hospitalized more than 48 hours Ventilator Associated Pneumonia (VAP) Occurs in an intensive care unit (ICU) patient more than 48 hours after endotrachial intubation and mechanical ventilation. 194 1. Micro of VAP/HAP 195 HAP/VAP-etiologic agents Streptococcus pneumonia inc. PRSP Hemophilus influenzae Anaerobes Legionella pneumophila Pseudomonas aeruginosa Methicillin-Resistant Staphylococcus aureus Acinetobacter, Stenotrophomonas, Burkholderia sps. ESBL+ (extended-spectrum B-lactamase) Klebsiella pneumonia/E. coli/Enterbacter sp./Serratia sp. Fungal and viral pathogens-rare 196 HAP/VAP-etiologic agents Early-onset HAP (first 5 days) more likely to be caused by antibiotic-sensitive pathogens Predisposing factors for patient colonization and infection with MDR pathogens include: Recent hospitalization Residence in a long-term care facility The presence of significant chronic disease Debility Recent antibiotic therapy 197 HAP/VAP-etiologic agents Gram-negative organisms still most common, >60%, including Pseudomonas, Klebsiella sp., Acinetobacter sp. Staphylococcus aureus now accounts for 20%-40% of episodes, most of which are now MRSA HAP/VAP due to MRSA is increasing worldwide Community-acquired MRSA (CA-MRSA) is also now a cause of HAP/VAP 198 2. Pathophysiology of HAP/VAP 199 HAP/VAP pathogenesis Outcome depends on: Number and types of colonizing pathogens that enter the LRT Host’s mechanical, cellular, and humoral defenses HAP-microaspiration ○ Sedation, vomiting, impaired swallowing, intubation during surgery VAP ○ Leakage around cuff ○ Inhalation of contaminated aerosols ○ Reflux of contaminated ventilator tubing condensate ○ Local trauma and inflammation from the endotracheal tube ○ Biofilm encased bacteria in the ETT lumen 200 HAP/VAPpathogenesis 201 3. Treatment plans for HAP/VAP (empiric) 202 HAP/VAP - Initial Empiric Antibiotic Therapy Assess risk factors for MDR + severity of illness Consider known pathogens endemic in YOUR intensive care unit/hospital Initiate antibiotic therapy: 3rd/4th generation antipseudomonal cephalosporin OR B-lactam/B-lactamase inhibitor OR • Cefepime plus Levofloxacin • Piperacillin/tazobactam plus Tobramycin • Meropenem plus Ciprofloxacin Carbepenem + aminoglycoside OR Antipseudomonal fluoroquinolone Consider extended-infusion vs. intermittent-infusion therapy 203 4. Antibiotic coverage for VAP/HAP 204 HAP/VAP Principles of Antibiotic Therapy Assess risks for MDR pathogens Obtain blood and sputum for smear and culture Begin empirical early, appropriate, and adequate antibiotic regimen Assess clinical response at 24-48 hours, review microbiologic data, de-escalate initial antibiotics if possible Nonresponders vs. responders 205 HAP/VAP-Treatment Narrowing the spectrum At 24-48 hours Minimizes complications of broad-spectrum antibiotics Once pathogen known, dual therapy not usually necessary Limiting the duration of therapy 7 days usually enough in responders who have no other complication (empyema, bacteremia with MRSA) 206 1. 2. 3. 4. Risks for non-TB mycobacteria Indications for steroids in PCP Micro involved compromised v. normal immune system Treatment for histoplasmosis 207 1. Risks for non-TB mycobacteria 208 NONTUBERCULOUS MYCOBACTERIA IN HIVINFECTED PATIENTS General categories Greatest risk with CD4 count < 50cells/mm3 Diagnosis requires clinical assessment and culture Sterile site Non-sterile site Infection vs Colonization 209 NONTUBERCULOUS MYCOBACTERIA IN HIVINFECTED PATIENTS Mycobacterium kansasii Most frequent isolated NTM Person-to-person transmission DOES NOT occur Tap water is the most likely source Louisiana, Illinois, Texas and Florida 210 2. Indications for steroids in PCP 211 PCP Prednisone indications ABG showing PaO2 < 70 mmHg (hypoxia) A-a oxygen gradient > 35 mmHg Duration for 21 days. 212 3. Micro involved compromised v. normal immune system 213 3a. Micro involved in compromised immune system 214 Fungal Infections - Compromised hosts Aspergillus sp. Zygomycetes Fusarium sp. Candida sp. Candida(Torulopsis) glabrata Curvularia lunata 215 Fungal Infections Equally in normal and Compromised Hosts Cryptococcus neoformans Nocardia asteroides Sporothrix schenckii Penicillium marneffei Geotrichum sp. 216 3b. Micro involved in normal immune system 217 Fungal Infections - Mostly in normal hosts Histoplasma capsulatum Blastomyces dermatitidis Coccidioides immitis Actinomyces sp. 218 Fungal Infections Equally in normal and Compromised Hosts Cryptococcus neoformans Nocardia asteroides Sporothrix schenckii Penicillium marneffei Geotrichum sp. 219 4. Treatment for histoplasmosis 220 Histoplasmosis COMLEX!!! Histoplasma capsulatum. Midwestern and central-eastern part of the USA. Worldwide distribution. Mostly rural areas and urban areas outbreaks with exposure to droppings of urban-living birds. Spelunkers who explore caves laden with bat. 221 Histoplasmosis Diagnosis Culture of expectorated sputum Culture of bronchoalveolar lavage Treatment Amphotericin B Itraconazole Efficacy of treatment can be evaluated by monitoring blood or urine Histoplasma antigen level Surgery for mediastinal fibrosis 222 1. 2. 3. 4. 5. Prophylaxis Compare RSV v. metapneumovirus Flu vaccine recommendations Treatments Trivalent v. quadvalent vaccines 223 1. Prophylaxis (influenza) 224 Viral Pneumonia Prevention Influenza vaccine. It is one of the greatest advances in public health. It is also one of the greatest failures (only 1/5 of people get it) Vaccine is trivalent. Two strains of type A and one of type B chosen each year on basis of those strains that emerge as the most prevalent at the end of the previous year. Given annually in fall. 225 Viral Pneumonia Prevention Zanamivir 10mg once daily Oseltamivir 75 mg once daily Start within 48h of exposure Duration varies for 10 days after household exposure or 7 days after exposure in other situations or 14 days in institutional settings 226 2. Compare RSV v. metapneumovirus 227 2a. RSV 228 Viral Pneumonia COMLEX!!!! Epidemiology RSV common in infants less than 6 months old. RSV most common cause of pneumonia in infants. Late fall, peaks in winter. Adenovirus infections occurs in childhood. More than 50 serotypes. Types 1 to 7 cause most cases of infection. 3,4,and 7 responsible for outbreaks. Tx is supportive care. 229 Viral Pneumonia COMLEX!!!! Clinical Manifestations Respiratory Syncytial Virus ○ Most common infection is URTI. ○ Most serious infection LRTI. ○ Causes bronchiolitis in children. ○ Adult infections are reinfections. URTI mostly. ○ Children at risk CF, congenital heart disease, malignant neoplasms, combined immunodeficiencies. Mortality up to 80%. 230 2b. Metapneumovirus 231 Human metapneumovirus Within Paramyxoviridae family 2 subfamilies Pneumovirinae and Paramyxovirinae It is an RNA virus. Subgroups A and B. 2 Subgroups A1, A2, B1, B2 Viral replication in the respiratory tract Transmission direct or close contact with contaminated secretion 232 Human metapneumovirus Epidemiology Ubiquitous Cause upper and lower tract infection Young children and older adults Seasonal variation late winter early spring in the USA Most children are infected by age 5 233 Human metapneumovirus Clinical Manifestations Incubation period is 5-6 days Children ○ Cough ○ Rhinitis ○ Fever ○ Wheezing ○ Range from bronchiolitis to ARDS 234 Human metapneumovirus Clinical Manifestations Adults ○ Cough ○ Nasal congestion ○ Rhinorrhea ○ Dyspnea ○ Hoarseness ○ Wheezing 235 Human metapneumovirus Diagnosis Reverse transcriptase-PCR Viral culture Serology with ELISA Treatment Supportive No clinical data on susceptibility to antivirals 236 3. Flu vaccine recommendations 237 Viral Pneumonia Prevention Influenza vaccine. It is one of the greatest advances in public health. It is also one of the greatest failures (only 1/5 of people get it) Vaccine is trivalent. Two strains of type A and one of type B chosen each year on basis of those strains that emerge as the most prevalent at the end of the previous year. Given annually in fall. Prevention High risk population ○ Cardiopulmonary patients ○ Diabetes mellitus ○ Chronic renal failure ○ Nursing home residents ○ Health care workers 238 4. Treatments (influenza) 239 Viral Pneumonia Treatment Zanamivir 10mg twice daily for 5 days Oseltamivir 75 mg twice daily for 5 days 240 5. Trivalent v. quadvalent vaccines 241 Viral Pneumonia Prevention Influenza vaccine. It is one of the greatest advances in public health. It is also one of the greatest failures (only 1/5 of people get it) Vaccine is trivalent. ○ Two strains of type A + ○ One strain of type B ○ Chosen each year on basis of those strains that emerge as the most prevalent at the end of the previous year. Given annually in fall. 242 5a. Trivalent vaccines 243 Viral Pneumonia Prevention Influenza vaccine. It is one of the greatest advances in public health. It is also one of the greatest failures (only 1/5 of people get it) Vaccine is trivalent. ○ Two strains of type A + ○ One strain of type B ○ Chosen each year on basis of those strains that emerge as the most prevalent at the end of the previous year. Given annually in fall. 244 5b. Quadvalent vaccines 245 Quadrivalent flu vaccine … FDA approved for 2013-2014 Fluzone Quadrivalent is the "first and only" 4-strain influenza vaccine option for children as young as 6 months. Fluarix Quadrivalent (GlaxoSmithKline), approved for adults and children aged 3 years or older FluMist (MedImmune), approved for adults and children aged 2 years or older. http://www.medscape.com/viewarticle/805587 246