Chiefs’ Inquiry Corner- 2/28/22

March 1, 2022

Chief residents of the NYU Langone Internal Medicine Residency give quick-and-easy, evidence-based answers to interesting questions posed by house staff, both in their clinics and on the wards.

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 Community-acquired bacterial aspiration pneumonia is suspected in patients in the community setting with new-onset or worsening respiratory symptoms (such as cough, increased sputum, new oxygen requirement, pleuritic chest pain) after an aspiration event or who have risk factors for aspiration. The diagnosis is primarily clinical; in addition to risk factors for aspiration and clinical presentation, chest imaging showing infiltrates consistent with aspiration (e.g., in dependent lung segments- superior or posterior basal segments of a lower lobe or the posterior segment of an upper lobe) can support the diagnosis. Historically, anaerobic organisms were believed to be the primary causative pathogens responsible for community-acquired bacterial aspiration pneumonia; however, more recent studies have indicated that aerobic bacteria are at least as common and clinically important.  Interestingly, treatment regimens with and without anaerobic coverage for patients with suspected aspiration pneumonia have not been compared in clinical trials. As a result, the Infectious Diseases Society of America (IDSA) guidelines only recommend adding anaerobic coverage only in the presence of or high suspicion for lung abscess or empyema. However, other experts add coverage against anaerobes along with standard community-acquired pneumonia for patients with a compelling clinical history (e.g., dysphagia, altered mental status), compatible imaging as above, and/or clinical signs of anaerobic pathogens (including putrid breath, severe periodontal disease, or dental caries).

References: Diagnosis and Treatment of Adults with Community-acquired Pneumonia
The gamma gap (also known as a protein gap) is the difference between the total serum protein and serum albumin (with such values obtained on comprehensive metabolic panels or hepatic panels). This ‘gap’ represents serum proteins other than albumin, which can include alpha-1, alpha-2, beta, and gamma globulins, and when elevated, is associated with a variety of inflammatory, infectious, and/or malignant conditions (for example, due to increased levels of acute phase reactants, complement proteins, or immunoglobulins). An elevated gamma gap, which is often assigned an arbitrary value of greater than or equal to 4.0 g/dL [there have not been any studies demonstrating an association between an elevated gamma gap of a particular magnitude and various clinical conditions] is an independent risk factor for all-cause mortality, even after adjusting for concomitant cardiovascular, pulmonary, and oncologic diseases, and its presence often triggers a workup for additional clinical entities such as malignancy or infection. Although an elevated gamma gap is clinically significant, there is no established threshold to inform further clinical decision making; the limited literature that does exist suggests there is a low yield from elated gamma gap as the sole rationale for further clinical workup. For example, one study demonstrated that a gamma gap of 4g/dL has a high specificity for HIV and HCV, but a threshold of 4g/dL was insensitive for both of these conditions, limiting its utility in ruling out either. With regards to MGUS, an elevated gamma gap is neither sensitive enough nor specific enough to justify further workup for this condition in the absence of additional clinical information, such as hemoglobin and eGFR. Another pair of studies demonstrated that among patients with a gamma gap >4 g/dL, <1% had monoclonal gammopathy or paraproteinemia ascribed to MGUS or lymphoproliferative disorders. Thus, elevated gamma gap can provide supporting evidence of an ongoing infectious, inflammatory, or malignancy-related condition in patients, and when present in a patient with one of those diagnoses, does portend increased mortality. However, its presence alone, in the absence of any other clinical signs or symptoms, should not trigger additional workup, as it has been repeatedly demonstrated to be of little utility or efficacy.

References: Gamma gap thresholds and HIV, hepatitis C, and monoclonal gammopathy
 Hyponatremia is a common feature of pneumonia caused by Legionella pneumophila. In one retrospective study comparing clinical features of legionella pneumonia to other etiologies of community-acquired pneumonia, hyponatremia (sodium < 131 mmol/L) was seen in 46% of patients with the former as compared to only in 14% of patients with the latter. The mechanism underlying this hyponatremia has not been completely elucidated, however. It has often been posited that dysregulation of antidiuretic hormone (ADH) in people with legionella pneumonia leads to syndrome of inappropriate diuretic hormone (SIADH) and subsequent hyponatremia. However, data to support this hypothesis remains sparse. In fact, additional studies have demonstrated upregulation of ADH in response to the stress of infection in people with legionella pneumonia. Other proposed mechanisms include renal salt wasting due to demonstrated direct nephrotoxic effects of cytokines and Legionella species on the kidney (with subsequent acute tubular necrosis or interstitial nephritis and sodium loss), as well as observational studies reporting increased levels of atrial natriuretic peptide (ANP) and B-type-natriuretic peptide (BNP) in patients with pneumonia, which can contribute to hyponatremia through increased natriuresis.

References: Hyponatremia and anti-diuretic hormone in Legionnaires’ disease