Gotway, Michael B.

An accurate differential diagnosis for diffuse lung disease can be confidently established by using a systematic approach to identify the predominant radiographic pattern, determine the distribution of disease, and assess for architectural or volume change.

Interlobular septal thickening (ILST) is a feature on chest computed tomography (CT) that is characterized by abnormal widening of the interlobular septa, which are thin connective tissues that separate secondary pulmonary lobules within the lung parenchyma. They contain pulmonary venules and lymphatic vessels. On CT, these septa are normally not visible in healthy patients. However, various pulmonary pathologic conditions can lead to ILST. If present, ILST can be categorized into 3 different patterns based on its morphologic appearance: smooth, nodular, and irregular/fibrotic. Each pattern occurs from different disease processes with little overlap. In this pictorial essay, we review common and rare etiologies for each type of ILST. For each disease, we discuss relevant pathophysiology, epidemiology, risk factors, symptoms, physical exam findings, labs, and management. Subsequently, we present the ILST features along with the distribution (eg, unilateral, bilateral, central, peripheral) and ancillary imaging findings that can support the diagnosis. Finally, characteristic and high-resolution figures are presented.

In a large, multicenter cohort of HIV and non–HIV immunocompromised patients with Pneumocystis jirovecii pneumonia, chest CT most commonly demonstrated diffusely distributed ground-glass opacity, with no imaging features distinguishing between immunocompromise etiology.

This article describes the typical and atypical chest imaging appearances of Pneumocystis jirovecii pneumonia.

Abstract Background Legionella pneumonia is an important cause of severe pneumonia, yet contemporary data describing its clinical phenotype, diagnostic patterns, and outcomes in the modern era are limited. Methods We conducted a retrospective multicenter cohort study of adults with laboratory-confirmed Legionella pneumonia across an integrated health system between January 2019 and September 2025. The primary outcome was 30-day mortality. Severe disease was defined as having a requirement for high-flow nasal cannula, noninvasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Univariate and multivariable logistic regression were used to identify predictors of mortality and severe disease. Results There were 344 patients with laboratory-confirmed Legionella pneumonia during the study period. The median age was 66.6 years, and 45.1% were immunocompromised. Most patients required hospital admission (94.2%), with 36.1% admitted to the intensive care unit; 22.7% required mechanical ventilation and 1.5% ECMO. Thirty- and 90-day mortality were 11.9% and 16.6%, respectively. In multivariable analysis, cirrhosis (OR 10.2, 95% CI 2.15–48.3, P = .003), immunocompromised status (odds ratio [OR] 2.24, 95% CI 1.05–4.77, P = .036), age (OR 1.03, 95% CI 1.00–1.06, P = .031), and lymphopenia at presentation (OR 2.09, 95% CI 1.02–4.24, P = .043) were independently associated with increased 30-day mortality. Among patients who were polymerase chain reaction (PCR) or culture positive, urinary antigen testing was positive in only 25.6%. Conclusions Legionella pneumonia was associated with substantial short-term mortality. Cirrhosis, age, immunocompromised status, and lymphopenia at presentation emerged as independent predictors of 30-day mortality, underscoring the importance of host vulnerability in determining outcomes.

ABSTRACT Background Solid organ transplant (SOT) recipients are at risk for Pneumocystis jirovecii pneumonia (PCP), yet how their clinical phenotype and outcomes compare with other immunocompromised patients without HIV remains poorly defined. Methods We conducted a multicenter retrospective cohort study of adults with proven or probable PCP from 2017 to 2025, including 95 SOT recipients and 588 non‐SOT, non‐HIV immunocompromised patients. The primary outcome was 90‐day mortality, secondary outcomes included new renal failure requiring dialysis, and 30‐day mortality. Outcomes were analyzed using inverse probability weighting (IPW) with winsorization to adjust for baseline differences. Results In unadjusted analysis, SOT recipients had lower 90‐day mortality (hazard ratio [HR]: 0.62, 95% CI 0.39–0.97, p = 0.037). After IPW with winsorization of extreme weights, SOT status remained associated with lower 90‐day mortality (HR: 0.32, 95% CI 0.13–0.76, p = 0.009), and 30‐day mortality (HR: 0.35, 95% CI: 0.14–0.92, p = 0.034). SOT recipients had higher odds of renal failure requiring dialysis in unadjusted analysis (OR: 3.49, 95% CI 1.94–6.14, p < 0.001), which persisted after IPW adjustment (OR: 1.62, 95% CI: 1.04–2.51, p = 0.032). Conclusions Despite higher rates of renal failure requiring dialysis, SOT recipients with PCP experienced significantly improved short‐ and intermediate‐term survival compared with other non‐HIV immunocompromised patients, underscoring the need for further investigation into transplant‐associated contributors to PCP outcomes.

This essay describes diagnostic criteria for and thoracic imaging appearances of acute and chronic coccidioidal pneumonia, unusual disease manifestations, and disseminated disease appearances.

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection increasingly recognized among non-HIV immunocompromised patients. In severe cases progressing to acute respiratory distress syndrome, venovenous extracorporeal membrane oxygenation (VV-ECMO) may serve as a rescue therapy. We conducted a retrospective multicenter review of 10 adult patients with proven or probable PCP who received VV-ECMO between 2017 and 2024. Seven of 10 patients survived to discharge, including all three HIV-positive patients and 4 of 7 non-HIV immunocompromised patients. The mean Respiratory ECMO Survival Prediction Score was –1.5, corresponding to a predicted survival of 33–57%. Multiorgan dysfunction was common, including renal failure requiring dialysis in 6 of 10 patients, need for neuromuscular blockade in 8 of 10, and pulmonary vasodilator use in 8 of 10. Despite high acuity and prolonged ECMO support, outcomes were favorable. These findings suggest that VV-ECMO may be a viable salvage therapy for select patients with severe PCP, including those without HIV.

Pneumocystis pneumonia (PCP) is a serious fungal infection affecting immunocompromised hosts. Decompensated cirrhosis leads to cirrhosis-associated immune dysfunction (CAID), a form of impaired cellular immunity that may predispose patients to opportunistic infections such as PCP. We conducted a retrospective review of 727 patients with proven or probable PCP from 2017 to 2025. Of these, 33 had decompensated cirrhosis. These patients were stratified into two groups: Cirrhosis Only (n = 16) and Cirrhosis with Additional Immunocompromising Conditions (n = 17). Among the patients with cirrhosis, the overall mortality was 48%, with the 90-day mortality reaching 57.6% (95% CI: 39.2–74.5%). Compared with those without cirrhosis, the patients with cirrhosis had a higher risk of mortality (OR: 4.08, 95% CI: 2.01–8.30, p < 0.001), increased intensive care unit (ICU) admission (87% vs. 42%, p < 0.001), and greater need for renal replacement therapy (54.6% vs. 7.5%, p < 0.001). These findings suggest that decompensated cirrhosis alone may represent a sufficient and underrecognized risk factor for PCP, with a high associated mortality. Given the preventable nature of this infection, future studies are needed to assess the incidence, define the risk, and investigate the role of prophylaxis in this vulnerable population.

Abstract Background Pneumocystis jirovecii pneumonia (PCP) is increasingly seen in patients who are non-HIV immunocompromised hosts, yet modern risk factors and outcomes are poorly recognized and defined. Methods A retrospective review was conducted of adult patients who met criteria for proven or probable PCP from 2017 to 2024 across a large academic multicenter health system. The primary outcome was mortality among cohorts, defined by etiology of immunosuppression through univariate and age-adjusted logistic regression. Secondary analyses included trends in annual diagnoses and testing patterns. Results A total of 701 patients met criteria for inclusion, representing one of the largest clinically characterized cohorts of PCP to date. The median age was 65 years (IQR, 54–73) and 62% were male. The most common risk groups were hematologic malignancy (32.2%), solid tumor cancers receiving chemotherapy (22.4%), and autoimmune disease with immunosuppression (17.7%). Annual PCP diagnoses increased at a rate of 15.8% (95% CI, 8.9%–23.2%) in parallel with increased testing. Only 5.4% of patients were receiving prophylaxis at the time of diagnosis. Overall mortality was 20% (95% CI, 17%–23%) and highest in cirrhosis (adjusted odds ratio, 6.24; 95% CI, 2.84–13.69; P &lt; .001). Conclusions PCP in the current era affects a broad range of patients who are immunocompromised, with high associated mortality and low rates of prophylaxis. Patients with solid tumors and those with cirrhosis are at particularly high risk of mortality. These findings highlight the need to reassess and redefine PCP prophylaxis guidelines in specific populations and our understanding of who is at risk.