The diagnostic usefulness and safety of transbronchial lung cryobiopsy for the evaluation of interstitial lung disease remain unclear.
This systematic review and metaanalysis aims to establish the ...diagnostic accuracy and yield of transbronchial cryobiopsy for interstitial lung diseases.
We searched MedLine, EMBASE, Cochrane Central Register of Controlled Trials, and conference proceedings to identify studies assessing the diagnostic accuracy (compared with surgical biopsy) or yield of transbronchial lung cryobiopsy for interstitial lung disease (from database inception to January 2016). The diagnostic accuracy and yield were quantified and stratified by the method of diagnosis determination (histologic interpretation in isolation vs. incorporation within a multidisciplinary discussion). The frequency of procedure-related complications was also assessed from these reports. For full-text studies, random-effects models were used to calculate pooled estimates of diagnostic accuracy, yield, and complication frequency.
Of 900 citations, 11 studies were selected for inclusion in this systematic review (7 full text, 4 abstracts). The selected studies reported on a total of 731 patients. No studies reported the diagnostic accuracy of transbronchial cryobiopsy. Diagnostic yield ranged from 74 to 98% when transbronchial cryobiopsy findings were interpreted in isolation, with a pooled estimate of 83% (95% confidence interval CI, 73-94). Diagnostic yield ranged from 51 to 98% when transbronchial cryobiopsy was reviewed within a multidisciplinary discussion, with a pooled estimate of 79% (95% CI, 65-93). Pooled estimates for pneumothorax and moderate/severe bleeding were 12% (95% CI, 3-21) and 39% (95% CI, 3-76), respectively.
The diagnostic accuracy of transbronchial lung cryobiopsy cannot be determined given the absence of studies directly comparing cryobiopsy diagnoses with diagnoses derived from surgical lung biopsies interpreted within multidisciplinary discussions. The histopathological and multidisciplinary discussion-based diagnostic yield of transbronchial cryobiopsy appears high, but with variable frequencies of complications dominated by pneumothorax and moderate-to-severe hemorrhage.
Progressive fibrosing interstitial lung disease (PF-ILD) is characterised by progressive physiological, symptomatic and/or radiographic worsening. The real-world prevalence and characteristics of ...PF-ILD remain uncertain.
Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015 and 2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation or any two of: relative FVC decline ≥5% and <10%, worsening respiratory symptoms or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression.
Of 2746 patients with fibrotic ILD (mean±sd age 65±12 years; 51% female), 1376 (50%) met PF-ILD criteria in the first 24 months of follow-up. PF-ILD occurred in 427 (59%) patients with idiopathic pulmonary fibrosis (IPF), 125 (58%) with fibrotic hypersensitivity pneumonitis (HP), 281 (51%) with unclassifiable ILD (U-ILD) and 402 (45%) with connective tissue disease-associated ILD (CTD-ILD). Compared with IPF, time to progression was similar in patients with HP (hazard ratio (HR) 0.96, 95% CI 0.79-1.17), but was delayed in patients with U-ILD (HR 0.82, 95% CI 0.71-0.96) and CTD-ILD (HR 0.65, 95% CI 0.56-0.74). Background treatment varied across diagnostic subtypes, with 66% of IPF patients receiving antifibrotic therapy, while immunomodulatory therapy was utilised in 49%, 61% and 37% of patients with CHP, CTD-ILD and U-ILD, respectively. Increasing age, male sex, gastro-oesophageal reflux disease and lower baseline pulmonary function were independently associated with progression.
Progression is common in patients with fibrotic ILD, and is similarly prevalent in HP and IPF. Routinely collected variables help identify patients at risk for progression and may guide therapeutic strategies.
Obesity is a health epidemic associated with greater morbidity and mortality in the general population. Mass loading of the thorax from obesity leads to a restrictive pulmonary defect that reduces ...lung capacity in obese individuals without pulmonary disease, and may exacerbate the restrictive pulmonary physiology that is characteristic of interstitial lung disease (ILD). The purpose of this study was to test the association of body mass index (BMI) with pulmonary function, functional capacity, and patient-reported outcomes (dyspnea and quality of life) in patients with ILD. We analyzed 3169 patients with fibrotic ILD from the Canadian Registry for Pulmonary Fibrosis. Patients were subcategorized as underweight (BMI<18.5 kg/m2), normal weight (18.5≤BMI<25), overweight (25≤BMI<30), obese I (30≤BMI<35), obese II (35≤BMI<40), and obese III (BMI>40). Analysis was performed using a linear regression with adjustment for common prognostic variables. Overweight and obese BMI categories were associated with worse pulmonary function, functional capacity, dyspnea, and quality of life compared to normal weight. This is likely a result of mass loading on the thorax, and we speculate that intentional weight-loss may improve lung function and functional capacity in obese patients with fibrotic ILD. The underweight BMI category was also associated with worse functional capacity compared to normal weight, which may reflect greater disease severity or the presence of other comorbidities. Future work should explore the clinical utility of BMI to improve patient outcomes.
•Increasing BMI is associated with worse pulmonary function, functional capacity, dyspnea, and quality of life in ILD.•Mass loading of the thorax in higher BMI categories could exacerbate the restrictive pulmonary defect characteristic of ILD.•Intentional weight-loss in overweight and obese patients may improve pulmonary function in addition to functional capacity.
Fibrotic interstitial lung disease (ILD) includes a large group of conditions that lead to scarring of the lungs. The lack of available 5-level EuroQol 5D (EQ5D) data has limited the ability to ...conduct economic evaluations in ILD. The purpose of this study was to develop and validate a mapping algorithm that predicts EQ5D utilities from commonly collected pulmonary function measurements (forced vital capacity FVC and diffusing capacity of the lung for carbon monoxide DLCO) in fibrotic ILDs.
EQ5D utility and pulmonary function measurements from the Canadian Registry for Pulmonary Fibrosis were included. Ordinary least squares (OLS), beta regression, two-part, and tobit models were used to map EQ5D utilities from FVC or DLCO. Model performance was assessed by comparing the predicted and observed utilities. Subgroup analyses were also conducted to test how well models performed across different patient characteristics. The models were then externally validated in the Australian Idiopathic Pulmonary Fibrosis Registry.
The OLS model performed as well as other more complex models (root mean squared error: 0.17 for FVC and 0.16 for DLCO). As with the other models, the OLS algorithm performed well across the different subgroups (except for EQ5D utilities < 0.5) and in the external validation cohort.
We developed a mapping algorithm that predicts EQ5D utilities from FVC and DLCO, with the intent that this algorithm can be applied to clinical trial populations and real-world cohorts that have not prioritized collection of health-related utilities. The mapping algorithm can be used in future economic evaluations of potential ILD therapies.
Abstract
Background
Comorbidities are frequent and have been associated with poor quality of life, increased hospitalizations, and mortality in patients with interstitial lung disease (ILD). However, ...it is unclear how comorbidities lead to these negative outcomes and whether they could influence ILD disease progression. The goal of this study was to identify clusters of patients based on similar comorbidity profiles and to determine whether these clusters were associated with rate of lung function decline and/or mortality.
Methods
Patients with a major fibrotic ILD (idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis, connective tissue disease-associated ILD, and unclassifiable ILD) from the CAnadian REgistry for Pulmonary Fibrosis (CARE-PF) were included. Hierarchical agglomerative clustering of comorbidities, age, sex, and smoking pack-years was conducted for each ILD subtype to identify combinations of these features that frequently occurred together in patients. The association between clusters and change in lung function over time was determined using linear mixed effects modeling, with adjustment for age, sex, and smoking pack-years. Kaplan Meier curves were used to assess differences in survival between the clusters.
Results
Discrete clusters were identified within each fibrotic ILD. In IPF, males with obstructive sleep apnea (OSA) had more rapid decline in FVC %-predicted (− 11.9% per year 95% CI − 15.3, − 8.5) compared to females without any comorbidities (− 8.1% per year 95% CI − 13.6, − 2.7; p = 0.03). Females without comorbidities also had significantly longer survival compared to all other IPF clusters. There were no significant differences in rate of lung function decline or survival between clusters in the other fibrotic ILD subtypes.
Conclusions
The combination of male sex and OSA may portend worse outcomes in IPF. Further research is required to elucidate the interplay between sex and comorbidities in ILD, as well as the role of OSA in ILD disease progression.
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.
Background
This multicentre, international, prospective cohort study evaluated whether patients with pulmonary sarcoidosis living in neighbourhoods with greater material and social disadvantage ...experience worse clinical outcomes.
Methods
The area deprivation index and the Canadian Index of Multiple Deprivation evaluate neighbourhood-level disadvantage in the US and Canada, with higher scores reflecting greater disadvantage. Multivariable linear regression evaluated associations of disadvantage with baseline forced vital capacity (FVC) or diffusing capacity of the lung for carbon monoxide (
D
LCO
) and linear mixed effects models for associations with rate of FVC or
D
LCO
decline, and competing hazards models were used for survival analyses in the US cohort, evaluating competing outcomes of death or lung transplantation. Adjustments were made for age at diagnosis, sex, race and smoking history.
Results
We included 477 US and 122 Canadian patients with sarcoidosis. Higher disadvantage was not associated with survival or baseline FVC. The highest disadvantage quartile was associated with lower baseline
D
LCO
in the US cohort (β = −6.80, 95% CI −13.16 to −0.44, p=0.04), with similar findings in the Canadian cohort (β = −7.47, 95% CI −20.28 to 5.33, p=0.25); with more rapid decline in FVC and
D
LCO
in the US cohort (FVC β = −0.40, 95% CI −0.70 to −0.11, p=0.007;
D
LCO
β = −0.59, 95% CI −0.95 to −0.23, p=0.001); and with more rapid FVC decline in the Canadian cohort (FVC β = −0.80, 95% CI −1.37 to −0.24, p=0.003).
Conclusion
Patients with sarcoidosis living in high disadvantage neighbourhoods experience worse baseline lung function and more rapid lung function decline, highlighting the need for better understanding of how neighbourhood-level factors impact individual patient outcomes.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has affected virtually all aspects of patient care. Health-care systems around the world ...are trying simultaneously to treat patients with COVID-19, prepare for its long-term impacts, and treat patients with other acute and chronic diseases. There are multiple ways that the COVID-19 pandemic will directly affect patients with fibrotic interstitial lung disease (ILD), particularly given their common risk factors for poor outcomes. Major issues for patients with ILD will include restricted access to key components of the diagnostic process, new uncertainties in the use of common ILD pharmacotherapies, limited ability to monitor both disease severity and the presence of medication adverse effects, and significantly curtailed research activities. The purpose of this review is to summarize how COVID-19 has impacted key components of the diagnosis and management of fibrotic ILD as well as to provide strategies to mitigate these challenges. We further review major obstacles for researchers and identify priority areas for future ILD research related to COVID-19. Our goals are to provide practical considerations to support the care of patients with ILD during the COVID-19 pandemic and to provide a road map for clinicians caring for these patients during future infectious disease outbreaks.
Functional capacity, as measured by the 6-min walk test (6MWT), is often reduced in fibrotic interstitial lung disease (ILD). This study evaluated longitudinal changes and the prognostic significance ...of 6MWT parameters, and explored change in oxygenation status as a physiological criterion to define disease progression in patients with fibrotic ILD.
What are the trajectories and prognostic value of 6MWT parameters in patients with fibrotic ILD?
Using prospective registries in Australia and Canada, patients with idiopathic pulmonary fibrosis (IPF) and non-IPF fibrotic ILD were stratified by the presence of criteria for progressive pulmonary fibrosis (PPF). The cumulative incidence of exertional and resting hypoxemia and changes in 6-min walk distance (6MWD) and composite indices (distance-saturation product and distance-saturation-oxygen product) were determined, with prognostic significance evaluated at the time of meeting criteria for PPF. New-onset exertional or resting hypoxemia was evaluated as another potential criterion for PPF.
Patients with IPF/PPF (n = 126) and non-IPF/PPF (n = 227) had a similar cumulative incidence of exertional hypoxemia and annualized decline in 6MWD and composite indices, which varied across each PPF criterion. Patients with IPF/non-PPF (n = 231) and non-IPF/non-PPF (n = 531) had a significantly lower incidence of hypoxemia than those with IPF/PPF, with an annualized increase in 6MWD and composite indices in the non-IPF/non-PPF group. Exertional or resting hypoxemia at the time of meeting criteria for PPF was independently associated with reduced transplant-free survival in IPF and non-IPF, adjusting for patient demographics and lung function. Adding new-onset exertional or resting hypoxemia as a physiological criterion reduced the median time to development of PPF from 11.2 to 6.7 months in IPF and from 11.7 to 5.6 months in non-IPF in patients who eventually met both definitions (P < .001 for both).
Patients with IPF/PPF and non-IPF/PPF have comparable deterioration in functional capacity. Oxygenation status provides prognostic information in PPF and may assist in defining disease progression in fibrotic ILD.
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