Pulmonary complication in the form of infectious and noninfectious disease remains the leading cause of morbidity and mortality in HIV-infected individuals. The spectrum of infectious complications appears to have changed since the introduction of combination antiretroviral drugs in the mid-1990s. In the early AIDS epidemic, respiratory failure due to Pneumocystis jiroveci pneumonia (PCP) was the leading cause of death. Although respiratory failure remains the most common indication for ICU admission, the rates of PCP have decline. Bacterial pathogens such as streptococcus pneumoniae, stapylococcus aureus and tuberculosis are common causes of respiratory failure. In fact, TB is responsible for 1 of 10 HIV/AIDS-related deaths worldwide. As HIV infection is becoming a chronic medical condition with a long-life expectancy, its association with noninfectious respiratory complications is also becoming widely recognized. Reactive airway disease, lung cancer (irrespective of smoking history) and pulmonary arterial hypertension (PAH) are increasingly becoming common indications for ICU admission in HIV-infected patients. Table 41–2 lists the pulmonary complications frequently encountered in critically ill HIV-infected patients.
Table 41–2Pulmonary complications associated with HIV infection. ||Download (.pdf) Table 41–2 Pulmonary complications associated with HIV infection.
|Infectious ||Noninfectious |
Other lung cancers
Alterations in host defense mechanisms, such as B lymphocyte dysfunction, abnormal secretion of immunoglobulin and mucociliary dysfunction, and other risk behaviors, such as tobacco use appear to increase the risk of pneumonia in HIV-infected patients irrespective of CD4 counts or antiretroviral use. Streptococcus pneumoniae and Mycobacterium tuberculosis are the leading cause of pneumonia but other bacterial, viral, and fungal (especially endemic fungi) pathogens are also prevalent.
Acute respiratory failure is commonly seen with viral and bacterial pneumonias, whereas tuberculosis, PCP, and other fungal infections have more of a subacute presentation. Chemoprophylaxis, vaccination history (pneumococcal and influenza), travel, and endemic exposures are clues when developing a differential diagnosis. Cough, fever, and dyspnea are the most common presenting symptoms.
Basic laboratory workup including lactate dehydrogenase (LDH) and sputum Gram stain and cultures (bacterial, mycobacterial, and fungal) should be obtained. Chest radiography (CXR) showing lobar pneumonia is suggestive of common community-acquired bacterial pathogens including Streptococcus pneumoniae, Hemophilus influenzae, and Staphylococcus aureus. Bronchoscopy is of limited value in establishing the diagnosis of bacterial pneumonia in HIV-infected patients with the exception of cases where there is high suspicion for mycobacterial disease or fungal process. Ancillary testing with urine antigen detection for Pneumococcus and Legionella have high specificity, but low sensitivity. For the endemic fungi, Histoplasma, Coccidioidomycosis, and Cryptococcus urine or serum antigen detection tests are available but have better yield in the setting of disseminated disease.
Community-acquired pneumonia coverage with third- or fourth-generation cephalosporin plus a respiratory fluoroquinolone (eg, levofloxacin or moxifloxacin) or macrolide (eg, azithromycin) should be initiated in patients presenting with suspected bacterial pneumonia. In severe respiratory failure requiring ICU admission, initial empiric coverage for gram-negative organisms (eg, Pseudomonas spp.) and resistant pathogens such as methicillin-resistant Staphylococcus aureus should be considered until culture data is available to guide therapy.
Pneumocystis Jiroveci Pneumonia
Since the widespread use of HAART and prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX), the prevalence of PCP-associated respiratory failure has decreased. Commonly presenting symptoms are nonproductive cough, fever, and anorexia evolving over 2 to 4 weeks in an AIDS patient (CD4 < 200). Hypoxia is the most common symptomatic and laboratory finding. Elevated LDH along with an alveolar-arterial (A-a) gradient more than 35 mm Hg is suggestive of PCP pneumonia. CXR commonly shows interstitial infiltrates with classic “butterfly” pattern or an atypical presentation with nodular, cavitary, or cystic lesions. In 20% of the cases, the CXR may be normal. Spontaneous pneumothorax in a patient with HIV should raise the suspicion for PCP.
Special stains of induced sputum for cysts or trophozoites are sensitive in less than 60% of cases; thus negative results warrant further investigation with bronchoscopy and bronchoalveolar lavage. Standard stains and techniques used for PCP diagnosis include Giemsa or modified Wright–Giemsa (also known as Diff–Quik), Gomori-methanamine silver, and immunofluorescent staining (direct fluorescent antibody). Recently, polymerase chain reaction (PCR) detection and measurement of 1-3 β-d-glucan levels are gaining wide acceptance in the diagnosis of PCP associated with AIDS although the utility in non-HIV patients is not yet well defined.
TMP-SMX remains the first-line therapeutic agent for PCP pneumonia. Adjunctive corticosteroid therapy is recommended to prevent lung injury in severe cases, clinically defined as PaO2 of less than 70 mm Hg or A-a oxygen gradient of more than 35 mm Hg on room air. For those patients who are intolerant to sulfa drugs, IV pentamidine is an alternate choice, but serious side effects including pancreatitis, renal failure, and hypoglycemia limit its use. Other alternative agents include the combination of clindamycin and primaquine, dapsone, and TMX or atovaquone. These regimens may not be ideal in critically ill patients, as primaquine, dapsone, and atovaquone are only available orally. Duration of therapy for PCP pneumonia is 21 days and clinical response is expected within 3 to 5 days. Treatment failure should be suspected if response lags more than 8 days. TMP-SMX is commonly associated with atypical adverse reactions such as fever, hepatitis, and leukopenia, which can be mistaken for treatment failure. The most common side effect reported with TMX-SMX is a rash.
HIV-infected individuals are at increased risk of developing serious complications from respiratory viruses especially with the influenza virus. During influenza season, HIV-infected patients are hospitalized at increased rates with influenza-related complications so aggressive preventive care with vaccination should be sought. Unlike the influenza virus, the significance of other viral pathogens such as herpes simplex virus (HSV), cytomegalovirus (CMV), and adenovirus when isolated from respiratory secretions is difficult to interpret and may represent viral shedding. For most patients, this may represent severe immunosuppression and is a sign of poor prognosis. The role of antiviral therapy has been debated and does not seem to show survival improvement.
HIV-Related Pulmonary Arterial Hypertension
The increased prevalence of PAH in HIV-infected patients has been recognized since the 1980s and seems to occur independent of the severity of immune deficiency or antiretroviral use. These patients usually present with clinical symptoms of chronic dyspnea and lower extremity edema. Doppler echocardiography shows elevated right ventricular and pulmonary pressures but confirmation of the diagnosis of PAH requires right heart catheterization showing mean pulmonary artery pressure more than 25 mm Hg at rest and normal pulmonary capillary wedge pressure less than 15 mm Hg. Conventional treatment with calcium channel blockers is not effective in HIV-PAH and antiretroviral therapy also does not seem to alter the disease course. Standard treatment agents available for PAH seem to have similar efficacy in HIV-infected patients but drug–drug interactions with antiretroviral agents (especially protease inhibitors, PIs) must be considered.