11/19/2012. The spectrum of pulmonary diseases in HIV-infected persons is broad.

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1 The spectrum of pulmonary diseases in HIV-infected persons is broad. HIV-associated Opportunistic infections Neoplasms Miscellaneous conditions Non HIV-associated Antiretroviral therapy (ART)-associated Opportunistic Infections Non-infectious Neoplasms Bacteria Pulmonary Kaposi sarcoma Mycobacteria Pulmonary Non-Hodgkin Lymphoma Pneumocystis Lung cancer Fungi Viruses Miscellaneous Conditions Parasites Lymphocytic interstitial pneumonitis Nonspecific interstitial pneumonitis Pulmonary arterial hypertension COPD Pulmonary fibrosis The spectrum of pulmonary diseases seen depends in part on the clinical setting. Inpatient Opportunistic infections > Non HIV-associated Intensive Care Unit (ICU) Opportunistic infections > Non HIV-associated Outpatient Non HIV-associated > Opportunistic infections 1

2 I spend the majority of my clinical time A. Inpatient care B. Critical care C. Outpatient care D. None of the above Case-based approach = Interactive (ARS) Outpatient focus Cases from my HIV/AIDS Chest Clinic and beyond Classic and challenging cases old and new Clinical and management pearls Professional society, National guidelines Which of the following is NOT more frequent in HIV+ than HIV-? A. Opportunistic Pneumonias (CAP, PCP, TB) B. COPD C. Asthma D. Lung cancer E. Pulmonary hypertension F. Pulmonary fibrosis Incidence per 1,000 person-years * p<0.05 Crothers. Am J Respir Crit Care Med 2011;183:388 2

3 Incidence per 1,000 person-years * p<0.05 * 1. Bacterial pneumonia 2. COPD 3. PCP 4. Asthma 5. TB 6. Lung cancer 7. Pulmonary hypertension 8. Pulmonary fibrosis Crothers. Am J Respir Crit Care Med 2011;183:388 CD4 = 400 cells/µl Case 2 5 days of fever, chills, chest pain, cough productive of purulent sputum, and dyspnea Physical examination Lungs Egophony, increased tactile fremitus, and bronchovesicular breath sounds (right) 3

4 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS) E. Other 1. Most frequent HIV-associated opportunistic pneumonia 2. Rates are 25-fold higher than among non-hivinfected Rates increase as CD4 cell count decreases 3. Presentation and diagnosis similar to non-hivinfected 4. Specific causative agent identified in 40-75% Streptococcus pneumoniae (40%) Haemophilus influenzae (10-15%) Staphylococcus aureus (5%) Beware community MRSA! Pseudomonas aeruginosa (5%) 1. USPHS Treatment Guidelines (2012) Similar to non-hiv-infected patients; beware levofloxacin monotherapy if TB also suspected 2. Preventive strategies Combination antiretroviral therapy Pneumococcal vaccine (CD4>200 cells/µl) Influenzae vaccine (annually) Trimethoprim-sulfamethoxazole (CD<200 cells/µl) Risk factor modification Cigarettes, injection and smoked illicit drugs CD4 < 100 cells/µl Several months of increasing dyspnea Exercise tolerance currently < 1 block Denies fever; no change in chronic cough Physical examination Lungs hyper-resonant, quiet breath sounds (bilateral) 4

5 Case 3 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS) E. Other 1. HIV-infected patients are subject to the entire spectrum of pulmonary disease The presence of HIV infection cannot exclude the possibility that the patient presents with a non- HIV-associated pulmonary disease. 2. HIV-infected cigarette smokers have an increased susceptibility to develop emphysema 1. Diagnosis and treatment identical to non-hivinfected patients Inhaled beta-agonists, anticholinergics Inhaled corticosteroids (GOLD III-IV) 2. In non-hiv, use of inhaled corticosteroids associated with increased risk of TB Shu. Medicine 2010;89: Brassard. Am J Respir Crit Care Med 2011;183: Supplemental O2 (PaO2 <55 mmhg, O2 <88%) Ann Intern Med 2011;155: Proc Am Thorac Soc 2012;9(1):9 18 5

6 Which of the following would you prescribe to an HIV+ patient with COPD who has frequent exacerbations? A. Anticholinergics & beta-agonists B. Supplemental O2 (if meets criteria) C. Azithromycin D. A and B E. All of the above Prospective, placebo-controlled (1:1), RCT Azithromycin 250 mg QD x 1 year COPD (FEV1/FVC <70%, post-bd FEV1 <80% predicted) On O2 or systemic glucocorticosteroids in last 1 year Time to 1 st COPD exacerbation Results: 572 (Azithro), 572 (placebo) Time to first exacerbation (p<0.001), frequency of exacerbations (p=0.01), HR for acute exacerbation per pt-yr (p<0.001) all favored Azithromycin but also increased hearing decrements N Engl J Med 2011;365: CD4 = 100 cells/µl 3 weeks of fever, cough (nonproductive) Acute onset of chest pain & dyspnea Physical examination Lungs quiet breath sounds 6

7 Case 5 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS) E. Other Presentation to clinic 5 days PTA Presentation to Emergency Room 1. PCP is the most common HIV-associated opportunistic pneumonia that presents with pneumothorax 2. Bilateral pneumothorax uncommon occurrence Associated with high mortality 1. Bronchoscopy with bronchoalveolar lavage (BAL) remains the gold standard diagnostic procedure Sensitivity = 89% to >98% (Broaddus 1985, Golden, 1986, Huang 1995) 2. Trimethoprim-sulfamethoxazole remains the first-line treatment (and prophylaxis) regimen 7

8 VACS study suggests that there is no increase in asthma incidence in HIV+ vs. HIV- Crothers. Am J Respir Crit Care Med 2011;183:388 One recent cross-sectional study suggests that the prevalence of asthma is high (20.6%) as is the prevalence of bronchodilator responsiveness (9.0%) Gingo. J Allergy Clin Immunol 2012;129: CD4 > 300 cells/µl (HIV RNA undetectable) Several months of increasing dyspnea Exercise tolerance currently < 1 block Denies fever; no change in chronic cough Physical examination Lungs hyper-resonant, quiet breath sounds (bilateral) 8

9 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS) E. Other 1. Pulmonary nodules are frequent incidental findings in HIV-infected persons. 215 HIV-infected men. Median CD4 count: 580 cells//µl 83% receiving antiretroviral medications Median age: 43 years; 17% current tobacco users Underwent screening cardiac CT 43% with incidental finding(s) on CT Pulmonary nodule(s) most common Required evaluation and/or follow-up No malignancies detected Crum-Cianflone. Am J Cardiol 2011;107(4): Fleischner Society, Radiological Society of North America Nodule size 4 mm High-risk patient (HIV+) Follow-up CT at 12 months; if unchanged, no further w/u* >4-6 mm Follow-up CT at 6-12 months then at months if no change* >6-8 mm Follow-up CT at 3-6 months then at 9-12 and 24 months if no change* >8 mm Follow-up CT at 3, 9, and 24 months, dynamic contrastenhanced CT, PET, and/or biopsy* Laurence * Huang, Increase MD in size mandates diagnostic w/u (e.g., biopsy, surgical removal The National Lung Screening Trial 52,454 persons at high risk for lung cancer at 33 US medical centers (8/02-4/04) Randomized to 3 annual screenings with low-dose CT or single-view PA chest radiography Followed through 12/09 Positive tests: CT (24.2%), CXR (6.9%) False-positive tests: CT (96.4%), CXR (94.5%) Incidence CA: RR = 1.13, 95% CI = N Engl J Med 2011;365:

10 CD4 < 50 cells/µl (HIV RNA ~2K copies/ml) Cough (occasional phlegm) Physical examination Lungs clear to auscultation 10

11 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS) E. Other 1. Clinical presentation and diagnosis compared to non-hiv-infected patients HIV-infected significantly younger (median age 50 vs. 68 years) Adenocarcinoma and squamous carcinoma predominate Stage IIIB/IV disease (77%) Outcomes probably comparable CD4 = 100 cells/µl Case 8 2 weeks of fever, cough (nonproductive), and dyspnea More recently, cough productive of purulent sputum Physical examination Lungs bilateral inspiratory crackles and focal findings (egophony, decreased breath sounds) 11

12 A. Bacterial pneumonia B. Pneumocystis pneumonia (PCP) C. COPD/emphysema D. Pulmonary Kaposi sarcoma (KS) E. Other 1. HIV-infected patients may present with more than one concurrent disease PCP diagnosed in 14 of 111 bacterial pneumonia cases (12.6%) Afessa. Chest Bacterial infection complicates PCP in ~10% 2. Beware: Concurrent diseases that present with identical clinical and radiographic features The spectrum of pulmonary diseases in HIVinfected persons is broad: HIV-associated Opportunistic infections (BP, PCP, TB, Cryptococcus) Neoplasms (KS, NHL, lung cancer) Miscellaneous conditions (LIP, NSIP, PAH, COPD, pulmonary fibrosis) ART-associated (HP, TB-IRIS, PCP-IRIS) PCP in ICU Non HIV-associated (Aspergillus PNA, asthma, Laurence pulmonary Huang, MD nodules, tracheal stenosis) Classic presentations of HIV-associated pulmonary diseases Presentations vary and overlap Patients may present with more than one concurrent pulmonary disease (PCP and BP) New era of ART-related pulmonary conditions THANKS! 12