Pleuroparenchymal fibroelastosis (PPFE) is a progressive and frequently fatal interstitial lung disease that involves the upper lobes. Although its cause remains unknown, the histopathologic evidence ...underlying PPFE bears striking resemblance to that of the pulmonary apical cap (PAC), a relatively common and benign entity. We describe the case of a patient with PAC that evolved into distinctly asymmetric PPFE over 6 years after unilateral surgical lung injury. Given the histologic similarity between these two conditions, we propose that these two entities underlie common biologic pathways of abnormal response to lung injury, with the presence of a PAC increasing susceptibility to the development of PPFE in the face of ongoing inflammatory insults. This case describes the histopathologic evolution of PAC to PPFE before and after an inciting injury.
Patients with fibrotic hypersensitivity pneumonitis (fHP) are frequently treated with immunosuppression to slow lung function decline; however, the impact of this treatment has not been studied ...across different types of antigen exposure.
In patients with fHP, do disease outcomes and response to treatment vary by antigen type?
A multicenter interstitial lung disease database (Canadian Registry for Pulmonary Fibrosis) was used to identify patients with fHP. The causative antigen was categorized as avian, mold, unknown, or other. Treatment was defined as mycophenolate ≥ 1,000 mg/d or azathioprine ≥ 75 mg/d for ≥ 30 days. Statistical analysis included t tests, χ2 tests, and one-way analysis of variance. Unadjusted and adjusted competing risks and Cox proportional hazards models were used to assess survival.
A total of 344 patients were identified with the following causative antigens: avian (n = 93; 27%), mold (n = 88; 26%), other (n = 15; 4%), and unknown (n = 148; 43%). Patient characteristics and lung function were similar among antigen groups with a mean FVC % predicted of 75 ± 20. The percent of patients treated with immunosuppression was similar between antigens with 58% of patients treated. There was no change in lung function or symptom scores with the initiation of immunosuppression in the full cohort. Immunosuppression was not associated with a change in survival for patients with avian or mold antigen (avian: hazard ratio, 0.41; 95% CI, 0.11-1.59; P = .20; mold: hazard ratio, 1.13; 95% CI, 0.26-4.97; P = .88). For patients with unknown causative antigen, survival was worse when treated with immunosuppression (hazard ratio, 2.65; 95% CI, 1.01-6.92; P = .047).
Response to immunosuppression varies by antigen type in patients with fHP. Additional studies are needed to test the role of immunosuppression in fHP, and particularly in those with an unknown antigen.
Clinical practice guidelines separately describe radiologic patterns of usual interstitial pneumonia (UIP) and fibrotic hypersensitivity pneumonitis (fHP), without direction on whether or how to ...apply these approaches concurrently within a single patient.
How can we integrate guideline-defined radiologic patterns to diagnose interstitial lung disease (ILD) and what are the pitfalls associated with described patterns that require reassessment in future guidelines?
Patients from the Canadian Registry for Pulmonary Fibrosis underwent detailed reevaluation in standardized multidisciplinary discussion. CT scan features were quantified by chest radiologists masked to clinical data, and guideline-defined patterns were assigned. Clinical data then were provided to the radiologist and an ILD clinician, who jointly determined the leading diagnosis.
Clinical-radiologic diagnosis in 1,593 patients was idiopathic pulmonary fibrosis (IPF) in 26%, fHP in 12%, connective tissue disease-associated ILD (CTD-ILD) in 34%, idiopathic pneumonia with autoimmune features in 12%, and unclassifiable ILD in 10%. Typical and probable UIP patterns corresponded to a diagnosis of IPF in 66% and 57% of patients, respectively. Typical fHP pattern corresponded to an fHP clinical diagnosis in 65% of patients, whereas compatible fHP was nonspecific and associated with CTD-ILD or IPAF in 48% of patients. No pattern ruled out CTD-ILD. Gas trapping affecting > 5% of lung parenchyma on expiratory imaging was an important feature broadly separating compatible and typical fHP from other patterns (sensitivity, 0.77; specificity, 0.91).
An integrated approach to guideline-defined UIP and fHP patterns is feasible and supports > 5% gas trapping as an important branch point. Typical or probable UIP and typical fHP patterns have moderate predictive values for a corresponding diagnosis of IPF and fHP, although occasionally confounded by CTD-ILD; compatible fHP is nonspecific.
BackgroundFibrotic interstitial lung disease (ILD) is frequently associated with abnormal oxygenation; however, little is known about the accuracy of oxygen saturation by pulse oximetry (SpO2) ...compared with arterial blood gas (ABG) saturation (SaO2), the factors that influence the partial pressure of carbon dioxide (PaCO2) and the impact of PaCO2 on outcomes in patients with fibrotic ILD.Study design and methodsPatients with fibrotic ILD enrolled in a large prospective registry with a room air ABG were included. Prespecified analyses included testing the correlation between SaO2 and SpO2, the difference between SaO2 and SpO2, the association of baseline characteristics with both the difference between SaO2 and SpO2 and the PaCO2, the association of baseline characteristics with acid-base category, and the association of PaCO2 and acid-base category with time to death or transplant.ResultsA total of 532 patients with fibrotic ILD were included. Mean resting SaO2 was 92±4% and SpO2 was 95±3%. Mean PaCO2 was 38±6 mmHg, with 135 patients having PaCO2 <35 mmHg and 62 having PaCO2 >45 mmHg. Correlation between SaO2 and SpO2 was mild to moderate (r=0.39), with SpO2 on average 3.0% higher than SaO2. No baseline characteristics were associated with the difference in SaO2 and SpO2. Variables associated with either elevated or abnormal (elevated or low) PaCO2 included higher smoking pack-years and lower baseline forced vital capacity (FVC). Lower baseline lung function was associated with an increased risk of chronic respiratory acidosis. PaCO2 and acid-base status were not associated with time to death or transplant.InterpretationSaO2 and SpO2 are weakly-to-moderately correlated in fibrotic ILD, with limited ability to accurately predict this difference. Abnormal PaCO2 was associated with baseline FVC but was not associated with outcomes.
Highlights ► During avian embryogenesis, the hypoxic drop in V ˙ O 2 did not cause a payment back of the O2 debt. ► At age E3, hypoxic hypometabolism was more prominent than at E5. ► The opposite was ...the case for heart rate (HR). ► In early embryos the O2 saving during hypometabolism can protect cardiac activity.
Recent clinical practice guidelines have addressed the diagnosis of idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (fHP). These disease-specific guidelines were ...developed independently, without clear direction on how to apply their respective recommendations concurrently within a single patient, where discrimination between these two fibrotic interstitial lung diseases represents a frequent diagnostic challenge. The objective of this review, created by an international group of experts, was to suggest a pragmatic approach on how to apply existing guidelines to distinguish IPF and fHP. Key clinical, radiologic, and pathologic features described in previous guidelines are integrated in a set of diagnostic algorithms, which then are placed in the broader context of multidisciplinary discussion to guide the generation of a consensus diagnosis. Although these algorithms necessarily reflect some uncertainty wherever strong evidence is lacking, they provide insight into the current approach favored by experts in the field based on currently available knowledge. The authors further identify priorities for future research to clarify ongoing uncertainties in the diagnosis of fibrotic interstitial lung diseases.
Previous studies have shown the importance of frailty in patients with fibrotic interstitial lung disease (ILD).
Is the Clinical Frailty Scale (CFS) a valid tool to improve risk stratification in ...patients with fibrotic ILD?
Patients with fibrotic ILD were included from the prospective multicenter Canadian Registry for Pulmonary Fibrosis. The CFS was assessed using available information from initial ILD clinic visits. Patients were stratified into fit (CFS score 1-3), vulnerable (CFS score 4), and frail (CFS score 5-9) subgroups. Cox proportional hazards and logistic regression models with mixed effects were used to estimate time to death or lung transplantation. A derivation and validation cohort was used to establish prognostic performance. Trajectories of functional tests were compared using joint models.
Of the 1,587 patients with fibrotic ILD, 858 (54%) were fit, 400 (25%) were vulnerable, and 329 (21%) were frail. Frailty was a risk factor for early mortality (hazard ratio, 5.58; 95% CI, 3.64-5.76, P < .001) in the entire cohort, in individual ILD diagnoses, and after adjustment for potential confounders. Adding frailty to established risk prediction parameters improved the prognostic performance in derivation and validation cohorts. Patients in the frail subgroup had larger annual declines in FVC % predicted than patients in the fit subgroup (−2.32; 95% CI, −3.39 to −1.17 vs −1.55; 95% CI, −2.04 to −1.15, respectively; P = .02).
The simple and practical CFS is associated with pulmonary and physical function decline in patients with fibrotic ILD and provides additional prognostic accuracy in clinical practice.
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