Sonavane, Sushilkumar K.

ABSTRACT Celiac disease (CD) is an autoimmune enteropathy with recognized extraintestinal manifestations. We describe a 55‐year‐old man with long‐standing, well‐controlled CD who developed progressive shortness of breath and cough. Imaging was indeterminate for usual interstitial pneumonia (UIP), and a surgical lung biopsy demonstrated a UIP pattern. Autoimmune serologies were negative, and no alternate etiologies for UIP were identified. With intermittent adherence to a gluten‐free diet and medical management including nintedanib, his disease progressed, ultimately leading to lung transplantation. This case raises the possibility of an association between CD and UIP of uncertain aetiology and should prompt further discussion as the relationship remains unclear. To contextualize this observation, we conducted a systematic review of published case reports evaluating pulmonary manifestations of celiac disease.

Objective: Pulmonary air trapping is critical for diagnosing and prognostication of various lung diseases. Expiratory CT imaging serves as an accessible method to assess air trapping, which correlates with small airway disease outcomes. Air trapping manifests as mosaic attenuation on inspiratory chest CT that is difficult for visual estimation. The primary aim of this study was to develop an automated tool to quantify mosaic attenuation on inspiratory CT and air trapping on paired expiratory CT. Secondary aims included comparing CT-derived parameters with PFT measurements and dyspnea scores. Methods: This retrospective analysis of noncontrast chest CTs from 2 academic hospitals was conducted between January 1, 2018, and December 31, 2019. Patients with paired inspiratory and expiratory CT chest scans and PFTs performed on the same day were included. A chest radiologist manually annotated lung parenchyma in a reference cohort. Several histogram-based metrics were computed from lung parenchymal CT values, with the maximum peak position showing the strongest correlation with manually determined thresholds. This threshold, derived from the histogram peak, was applied in the adaptive thresholding process to quantify mosaic attenuation and air trapping. Results: We analyzed 267 patients (65.5% female, median age 68). Most exhibited normal physiological patterns (44.0%). Patients with elevated residual volume (RV) by PFTs (28.1%) had significantly higher inspiratory CT mosaic attenuation (1629.6 vs. 1311.5 mL, P <0.01) and expiratory CT air trapping volumes (1413.7 vs. 886.2 mL, P <0.01). Correlation analyses demonstrated strong relationships between CT-derived mosaic attenuation and air trapping measures and RV. The correlation with PFT parameters was even stronger in subgroup analyses in patients with obstructive PFT patterns. These models had good predictive ability for an abnormal RV (AUC of 0.92, sensitivity of 72.4%, and specificity of 92.0%) and clinical utility based on good correlation with the mMRC dyspnea score ( r =0.71; 95% CI: 0.65-0.77). Conclusions: This automated adaptive thresholding on inspiratory and expiratory chest CT scans showed a high correlation of lung volume and air trapping parameters with PFTs, revealing that measures of lung function have a complex interplay with air trapping.

Abstract Rationale Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) are associated with significant morbidity and mortality. Whether mucus plugs are associated with prospective exacerbations has not been examined extensively. Objectives To examine associations between mucus plugs on chest computed tomography (CT) and future moderate-to-severe AEs in two independent cohorts with spirometrically-confirmed COPD. Methods Mucus plugs were visually identified on baseline chest computed tomography scans from smokers with Global Initiative for Chronic Obstructive Lung Disease grade 2–4 COPD enrolled in two multicenter cohort studies: ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and COPDGene (Genetic Epidemiology of COPD). Associations between ordinal mucus plug score categories (0, 1–2, and ≥3) and prospectively ascertained AEs, defined as worsening respiratory symptoms requiring systemic steroids and/or antibiotics (moderate to severe) and/or emergency room visit or hospitalization (severe), were assessed using multivariable-adjusted zero-inflated Poisson regression; subjects were exacerbation-free at enrollment. Measurements and Main Results Among 3,250 participants in COPDGene (mean age ± SD, 63.7 ± 8.4 yr; FEV1, 50.6 ± 17.8% predicted; 45.1% female) and 1,716 participants in ECLIPSE (age, 63.3 ± 7.1 yr; FEV1, 48.3 ± 15.8% predicted; 36.2% female), 44.4% and 46.0% had mucus plugs, respectively. The incidence rates of AEs were 61.0 (COPDGene) and 125.7 (ECLIPSE) per 100 person-years. Relative to those without mucus plugs, the presence of 1–2 and ≥3 mucus plugs was associated with increased risk (adjusted rate ratio [aRR], 1.07 [95% CI, 1.05–1.09] and 1.15 [1.1–1.2] in COPDGene; aRR, 1.06 [95% CI, 1.02–1.09] and 1.12 [1.04–1.2] in ECLIPSE, respectively) for prospective moderate to severe AEs. The presence of 1–2 and ≥3 mucus plugs was also associated with increased risk for severe AEs during follow-up (aRR, 1.05 [95% CI, 1.01–1.08] and 1.09 [1.02–1.18] in COPDGene; aRR, 1.17 [95% CI, 1.07–1.27] and 1.37 [1.15–1.62] in ECLIPSE, respectively). Conclusions Computed tomography–detected mucus plugs are associated with an increased risk for future COPD AEs.

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