DLCO Research Articles

Prevalence, causes, and clinical associations of anemia in patients with systemic sclerosis: A cohort study.

Anemia is considered a risk factor of severity in systemic sclerosis. Yet, limited data are available on the frequency and causes of anemia in systemic sclerosis. The objectives of our study were to determine the frequency and causes of anemia in systemic sclerosis, to analyze the clinical and biological characteristics of patients with anemia, and to assess the association between anemia and systemic sclerosis prognosis. We conducted a prospective single-center study from January 2017 to May 2022. Patients underwent a hemoglobin assay and a standardized etiological workup to determine the causes of anemia at the initial visit. Clinical and biological parameters were compared between patients with anemia and those with normal hemoglobin levels. We followed up patients until May 2023 and compared their survival. A total of 502 systemic sclerosis patients, including 107 diffuse cutaneous systemic sclerosis, were included. At enrollment, 100 patients had anemia. The primary cause of anemia was iron deficiency (40%). Among the 32 patients with iron deficiency-associated anemia who underwent gastrointestinal exploration, 56% had digestive bleeding, with upper gastrointestinal tract involvement being the main cause (90%). Patients with anemia at enrollment had higher systemic sclerosis severity scores and more gastrointestinal symptoms compared to patients without anemia (p < 0.05). They exhibited higher systolic pulmonary artery pressure, lower anemia-corrected diffusing capacity for carbon monoxide, and lower forced vital capacity (p < 0.05). During follow-up, 65 patients (14.8%) died. After adjusting for age, systemic sclerosis subtypes, forced vital capacity, and pulmonary arterial hypertension, anemia at inclusion was associated with a higher mortality rate (hazard ratio: 1.94 (95% confidence interval: 1.39-2.48), p = 0.02). Our study shows a high frequency of anemia among patients with systemic sclerosis. Most anemias are due to iron deficiency, and gastrointestinal exploration can identify bleeding in the majority of the cases. In addition, our study confirms that systemic sclerosis patients with anemia have a more severe disease and a higher mortality rate.

One-year follow-up of COVID-19 recoverees with impaired pulmonary function: A prospective cohort study

Decreased diffusion capacity for carbon monoxide (DLCO) is the most prevalent pulmonary testing abnormality among COVID-19 recoverees. We prospectively followed 51 individuals with impaired DLCO at an average of ∼3 months following COVID-19 and re-examined them at one year. At follow-up, mean DLCO increased from 68.0 % to 72.6 % (p = 0.002); while 33 % of the cohort experienced a clinically significant rise (>10 points) in DLCO, only 29 % normalized their values. While DLCO change did not correlate with symptoms, lack of improvement was more prevalent among individuals with obesity. Regardless of COVID-19 severity, a substantial proportion continued to exhibit DLCO impairment at 1-year.

Persistence of Diffusion Capacity Impairment and Its Relationship with Dyspnea 12 Months after Hospitalization for COVID-19.

Background: Dyspnea is a common persistent symptom after acute coronavirus disease 2019 illness (COVID-19). One potential explanation for post-COVID-19 dyspnea is a reduction in diffusion capacity. This longitudinal study investigated diffusion capacity and its relationship with dyspnea on exertion in individuals previously hospitalized with COVID-19. Methods: Eligible participants had been hospitalized for the treatment of acute COVID-19 and were assessed at 6 weeks, 6 months, and 12 months after discharge. Pulmonary function testing, diffusion capacity of carbon monoxide (DLCO), blood gas analysis and the level of dyspnea (Borg scale; before and after a 6 min walk test [6 MWT]) were performed. Participants were divided into subgroups based on the presence or absence of dyspnea during the 6 MWT at 12 months after hospitalization. Results: Seventy-two participants (twenty-two female, mean age 59.8 ± 13.5 years) were included. At 12 months after discharge, 41/72 participants (57%) had DLCO below the lower limit of normal and 56/72 (78%) had DLCO < 80% of the predicted value. Individuals with exertional dyspnea had significantly lower DLCO than those without exertional dyspnea (p = 0.001). In participants with DLCO data being available at three timepoints over 12 months (baseline, 6 months, and 12 months) after discharge (n = 25), DLCO improved between 6 weeks and 6 months after hospital discharge, but not thereafter (p = 0.017). Conclusions: About 2/3 of the post-COVID individuals in this study had impaired diffusion capacity at 12 months after hospital discharge. There was an association between persisting dyspnea on exertion and significantly reduced DLCO. Impaired diffusion capacity improved over the first 6 months after hospitalization but not thereafter.

Clinical analysis of COVID-19 in patients with preexisting interstitial lung abnormalities

Objective: To describe the clinical characteristics of SARS-CoV-2 infected patients with interstitial lung abnormalities (ILA) during the COVID-19 pandemic. Methods: We respectively enrolled ILA patients who had been regularly followed up in Peking Union Medical College Hospital for more than six months since January 2021. Clinical data of these ILA patients were collected after the outbreak of COVID-19 pandemic (from December 2022 to January 2023), thirty-eight patients with preexisting ILA were enrolled. Among them, there were 34 ILA patients (20 males and 14 females) who were infected with SARS-CoV-2 during this period, with an average age of (64.0±8.8) years old (range: 41-80). There were 12 (35.3%) ILA patients who were suffered from COVID-19(pneumonia group) and others were the non-pneumonia group. The clinical characteristics, including vaccination status, features of COVID-19 and outcomes of the two groups were compared. Results: Regarding the subcategories of ILA, there were 7 cases of subpleural fibrotic ILA, 10 cases of subpleural non-fibrotic ILA, and 17 cases of non-subpleural ILA. Before SARS-CoV-2 infection, the average pulse oxygen saturation at rest was (97.38±0.87)% (range: 96%-99%); average forced vital capacity (FVC) was (97.6±18.1)% predicted (range: 65%-132%); and average diffusion capacity for carbon monoxide (DLCO) was (76.2±16.3)% predicted (range: 53%-108%). Nineteen patients had been vaccinated with 3 doses of SARS-CoV-2 vaccines, and 5 of them developed COVID-19. One patient had received one dose of vaccine and did not develop COVID-19. The other 14 patients had not been vaccinated, and seven of them developed COVID-19. Of the 12 patients with COVID-19, six were diagnosed with severe COVID-19, and the other 6 ILA patients were diagnosed with moderate COVID-19. Among them, 1 patient was complicated by deep vein thrombosis of left lower limb. All 6 patients with severe COVID-19 who were cured after systemic corticosteroids. As for the other six moderate COVID-19 patients, all were cured and/or improved greatly: two were treated with short-term oral corticosteroids, one was prescribed a dose of compound betamethasone, and the other two were not treated with systemic corticosteroids. Conclusion: Patients with ILA were predisposed to develop COVID-19 after infection with SARS-CoV-2, and more than half of them had severe COVID-19.

Impact of interstitial lung disease on left ventricular myocardial function.

Interstitial lung disease (ILD) comprises a wide variety of pulmonary parenchymal disorders within which progressive fibrosing ILD (PF-ILD) constitutes a phenotypic subset. By use of speckle tracking-based strain analysis we aimed to evaluate the degree of left ventricular (LV) dysfunction in progressive vs. non-progressive fibrosing ILD (non-PF-ILD). A total of 99 ILD patients (mean age 63.7 ± 13.5 years, 37.4% female), composed of 50 PF-ILD and 49 non-PF-ILD patients, and 33 controls were prospectively enrolled and underwent conventional and speckle tracking echocardiography. Additional laboratory and pulmonary function testing, as well as six-minute walk test were performed. As compared to the non-PF-ILD cohort, PF-ILD patients exhibited a significantly impaired forced vital capacity (2.4 ± 1.0l vs. 3.1 ± 0.9l, p = 0.002), diffusion capacity for carbon monoxide (DLCO, 25.6 ± 16.3% predicted vs. 43.6 ± 16.67% predicted, p <0.001) and exercise capacity response as measured by the six-minute walk test distance (268.1 ± 178.2m vs. 432.6 ± 94.2m, p <0.001). Contrary to conventional echocardiographic LV parameters, both regional and global longitudinal LV strain measurements were significantly altered in ILD patients as compared to controls. No differences in LV strain were found between both patient groups. Significant correlations were observed between global longitudinal strain, on the one hand, and systemic inflammation markers, total lung capacity (TLC) and DLCO, on the other hand (high-sensitivity C-reactive protein: Pearson´s r = -0.30, p< 0.001; interleukin-6: Pearson´s r = -0.26, p = 0.007; TLC % predicted: Pearson´s r = 0.22, p = 0.02; DLCO % predicted: Pearson´s r = 0.21, p = 0.02). ILD is accompanied by LV dysfunction. LV functionality inversely correlates with the severity of the restrictive ventilatory defect and inflammation marker levels. These observations support the assumption of persistent low-grade systemic inflammation that may link systemic cardiovascular function to ILD status.

Resolving the Complexity: A Comprehensive Review on Carbon Monoxide Diffusion Capacity in Chronic Obstructive Pulmonary Disease Patients.

This review comprehensively examines the intricate relationship between carbon monoxide (CO) diffusion capacity and chronic obstructive pulmonary disease (COPD). COPD, comprising chronic bronchitis and emphysema, presents a substantial global health burden, necessitating a nuanced understanding of pulmonary function parameters for effective diagnosis and management. The review delves into the physiological underpinnings, measurement techniques, and factors influencing CO diffusion capacity, emphasizing its pivotal role in assessing alveolar gas exchange efficiency. Key findings elucidate correlations between altered diffusion capacity and the severity of COPD, providing clinicians with valuable insights into disease progression. Considerations of age, gender, and ethnic disparities in normal CO diffusion capacity values highlight the importance of personalized interpretations. The clinical implications extend beyond diagnosis, influencing COPD management and prognostication, with potential applications in predicting treatment response. The review outlines avenues for future research, including advancements in measurement technologies and the exploration of novel imaging modalities and biomarkers. Ultimately, this review serves as a foundation for refining diagnostic approaches and treatment strategies and enhancing patient care in the dynamic landscape of COPD.

Antifibrotics in rheumatoid arthritis-associated interstitial lung disease - real-world data from a nationwide cohort.

Interstitial lung disease (ILD) is the most common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with an increased mortality. Clinical trials have shown that antifibrotics (nintedanib and pirfenidone) can slow the progression of connective tissue disease-associated ILD. This study aims to evaluate the effectiveness and tolerability of antifibrotics in a national, real-world cohort of patients with RA-ILD. We conducted an observational multicenter study of RA-ILD patients treated with antifibrotics, who were prospectively followed in Reuma.pt. Demographic and clinical data, pulmonary function tests (PFTs) results and adverse events (AEs) were collected. A linear mixed model with random intercept was used to compare PFT results within 12 (±6) months before to 12 (±6) months after antifibrotic initiation. Drug persistence was evaluated using Kaplan-Meier curves. We included 40 RA-ILD patients, 27 (67.5%) initially treated with nintedanib and 13 (32.5%) with pirfenidone. Most of the patients were female (55%), and current or past smokers (52.5%). At antifibrotic initiation, mean age was 70.9 ± 7.1 years and median ILD duration 5.0 [IQR 2.3-7.5] years. A total of 20 patients were included in effectiveness analysis, with the use of antifibrotics interrupting the decline of forced vital capacity (FVC; decline 300 ± 500 mL in the year before antifibrotic initiation vs. improvement of 200 ± 400 mL in the year following antifibrotic initiation, p=0.336) and total lung capacity (TLC; decline 800 ± 300 mL in the year before antifibrotic initiation vs. improvement of 600 ± 900 mL in the year following antifibrotic initiation, p=0.147). However, diffusion capacity for carbon monoxide remained in decline (3% decline in the year before antifibrotic initiation vs. 2.9% decline in the year following antifibrotic initiation, p=0.75). AEs were reported in 16 (40%) patients and led to drug discontinuation in 12 (30%). Median duration of drug persistence was 150.3 weeks (95 %CI 11.0-289.6), with no difference between nintedanib and pirfenidone (p = 0.976). This study with real-world data corroborates the usefulness of antifibrotics in stabilizing lung function, based on FVC and TLC. However, AEs were frequently reported and were the main cause for drug discontinuation.

Bosentan and ambrisentan in the treatment of idiopathic pulmonary fibrosis: a meta-analysis.

The aim is to showcase the effectiveness and safety of bosentan or ambrisentan in individuals diagnosed with idiopathic pulmonary fibrosis (IPF) and offer fresh evidence for the management of this condition. For this research, we conducted a meta-analysis of randomized controlled trials by searching various databases, including the Cochrane Library, Excerpta Medica Database, PubMed, and Web of Science. The retrieval was conducted until November 2021. We analyzed the variances in 6-minute walk distance (6MWD), death, diffusion capacity for carbon monoxide (DLCO), forced vital capacity (FVC), hospitalization, IPF worsening, mean pulmonary arterial pressure, serious adverse events (SAEs), Short Form-36 improved, and St. George's Respiratory Questionnaire between the treatment and control groups. A sum of six studies involving 1,928 participants were found to meet the inclusion criteria. The quality of evidence was high. The control group had significantly higher values for 6MWD, DLCO, and FVC compared to the ambrisentan treatment group. The rates of hospitalization and IPF worsening were considerably greater in comparison with the control group. The bosentan group exhibited significantly reduced rates of hospitalization and IPF worsening in comparison with the control group. Both drugs did not cause any raising in death or SAEs when in comparison with the control group. The findings of this research validate the effectiveness and safety of bosentan for treating IPF patients. This medication can enhance the quality of life for individuals with IPF without causing any significant increase in SAEs. However, it does not have a notable influence on the long-term prognosis. The findings of this research do not endorse the utilization of ambrisentan in individuals diagnosed with IPF.

Lung Function in Fontan Patients Over a Ten-Year Period: Is the Fontan Circulation Impairing Lung Development?

Few studies have investigated how the Fontan circulation affects lung function, and no studies have investigated the development of lung function over longer time in these patients. We aimed to describe the development of lung function in Fontan patients over a 10-year period. Pulmonary function tests (PFT), including spirometry and diffusion capacity for Carbon Monoxide (DLCO) and Nitric Oxide (DLNO), were conducted in a Danish Fontan cohort in 2011 (PFT-I). In 2021, re-investigations were performed (PFT-II). We investigated changes in percent predicted (%pred) lung function from PFT-I to PFT-II. Patients were categorized into a pediatric group (age under 18 at PFT-I) and an adult group (age 18 or older at PFT-I). Out of the 81 patients completing PFT-I, 48 completed PFT-II. In the pediatric group (32 patients), there were significant declines in %pred forced expiratory volume in 1s (99.7 (92.4, 104.4)–89.3 (84.9, 97.2), p < 0,001), forced vital capacity (98.3 (87.8, 106.1)–96.7 (86.7, 100.6), p = 0.008), and alveolar volume (95.5 (89.5, 101.6)–89.5 (79.7, 93.2), p < 0.001). The corresponding measurements remained stable in the adult group. However, the median %pred DLNO significantly declined in the adult group (58.4 (53.3, 63.5)–53.7 (44.1, 57.3), p = 0.005). Over a 10-year period, several lung function parameters declined significantly in the younger Fontan patients, suggesting possible impairments in lung development during growth. The decline in %pred DLNO in the adult patient group indicates deterioration of the membrane component of diffusion capacity, implying that the Fontan circulation might negatively affect the alveolar membrane over time.

Multidisciplinary-derived clinical score for accurate prediction of long-term mortality in fibrotic lung disease patients

BackgroundIdiopathic pulmonary fibrosis (IPF) stands out as one of the most aggressive forms of interstitial lung diseases (ILDs), currently without a definitive cure. Multidisciplinary discussion (MDD) is now considered a cornerstone in diagnosing and differentiating ILD subtypes. The Gender-Age-Physiology (GAP) score, developed to assess IPF prognosis based on sex, age, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO), is limited in not considering dyspnea and functional impairment during the walking test. We proposed a MDD-based clinical score for mortality prediction among those patients.MethodsFrom December 2018 to December 2019, we enrolled ILD patients with IPF and non-IPF and followed-up them till December 2020. Based on DLCO, modified Medical Research Council (mMRC) Dyspnea Scale, and six-minute walking test (6MWT) distance, a functional score was developed for mortality prediction.ResultsWe enrolled 104 ILD patients, 12 (11.5%) died by the one-year follow-up. In receiver operating characteristic (ROC) curve analysis, DLCO (% predicted) was the most accurate variable predicting one-year mortality with an area under curve (AUC) of 0.88 (95% confidence interval [CI] = 0.80–0.94), followed by mMRC Dyspnea Score (AUC = 0.82 [95% CI = 0.73–0.89]), 6MWT distance (AUC = 0.80 [95% CI = 0.71–0.88]), and GAP score (AUC = 0.77 [95% CI = 0.67–0.84]). Only the GAP score (hazard ratio [HR] = 1.55, 95% CI = 1.03–2.34, p = 0.0.37) and functional score (HR = 3.45, 95% CI = 1.11–10.73, p = 0.032) were significantly associated with one-year mortality in multivariable analysis.ConclusionThe clinical score composite of DLCO, mMRC Dyspnea Scale, and 6MWT distance could provide an accurate prediction for long-term mortality in ILD patients, laying out a helpful tool for managing and following these patients.

Factors Associated with the Discrepancy between Exercise Capacity and Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease.

Exercise capacity is associated with lung function decline in chronic obstructive pulmonary disease (COPD) patients, but a discrepancy between exercise capacity and airflow limitation exists. This study aimed to explore factors contributing to this discrepancy in COPD patients. Data for this prospective study were obtained from the Korean COPD Subgroup Study. The exercise capacity and airflow limitation were assessed using the 6-minute walk distance (6-MWD; m) and forced expiratory volume in 1 second (FEV1). Participants were divided into four groups: FEV1 &gt;50%+6-MWD &gt;350, FEV1 &gt;50%+6- MWD ≤350, FEV1 ≤50%+6-MWD &gt;350, and FEV1 ≤50%+6-MWD ≤350 and their clinical characteristics were compared. A total of 883 patients (male:female, 822:61; mean age, 68.3±7.97 years) were enrolled. Among 591 patients with FEV1 &gt;50%, 242 were in the 6-MWD ≤350 group, and among 292 patients with FEV1 ≤50%, 185 were in the 6-MWD &gt;350 group. The multiple regression analyses revealed that male sex (odds ratio [OR], 8.779; 95% confidence interval [CI], 1.539 to 50.087; p=0.014), current smoking status (OR, 0.355; 95% CI, 0.178 to 0.709; p=0.003), and hemoglobin levels (OR, 1.332; 95% CI, 1.077 to 1.648; p=0.008) were significantly associated with discrepancies in exercise capacity and airflow limitation in patients with FEV1 &gt;50%. Meanwhile, in patients with FEV1 ≤50%, diffusion capacity of carbon monoxide (OR, 0.945; 95% CI, 0.912 to 0.979; p=0.002) was significantly associated with discrepancies between exercise capacity and airflow limitation. The exercise capacity of COPD patients may be influenced by factors other than airflow limitation, so these aspects should be considered when assessing and treating patients.

Morphine for treatment of cough in idiopathic pulmonary fibrosis (PACIFY COUGH): a prospective, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial

Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease, with most patients reporting cough. Currently, there are no proven treatments. We examined the use of low dose controlled-release morphine compared with placebo as an antitussive therapy in individuals with idiopathic pulmonary fibrosis. The PACIFY COUGH study is a phase 2, multicentre, randomised, double-blind, placebo-controlled, two-way crossover trial done in three specialist centres in the UK. Eligible patients aged 40-90 years had a diagnosis of idiopathic pulmonary fibrosis within 5 years, self-reported cough (lasting >8 weeks), and a cough visual analogue scale (VAS) score of 30 mm or higher. Patients were randomly assigned (1:1) to placebo twice daily or controlled-release morphine 5 mg orally twice daily for 14 days followed by crossover after a 7-day washout period. Patients were randomised sequentially to a sequence group defining the order in which morphine and placebo were to be given, according to a computer-generated schedule. Patients, investigators, study nurses, and pharmacy personnel were masked to treatment allocation. The primary endpoint was percentage change in objective awake cough frequency (coughs per h) from baseline as assessed by objective digital cough monitoring at day 14 of treatment in the intention-to-treat population, which included all randomised participants. Safety data were summarised for all patients who took at least one study drug and did not withdraw consent. This study was registered at ClinicalTrials.gov, NCT04429516, and has been completed. Between Dec 17, 2020, and March 21, 2023, 47 participants were assessed for eligibility and 44 were enrolled and randomly allocated to treatment. Mean age was 71 (SD 7·4) years, and 31 (70%) of 44 participants were male and 13 (30%) were female. Lung function was moderately impaired; mean forced vital capacity (FVC) was 2·7 L (SD 0·76), mean predicted FVC was 82% (17·3), and mean predicted diffusion capacity of carbon monoxide was 48% (10·9). Of the 44 patients who were randomised, 43 completed morphine treatment and 41 completed placebo treatment. In the intention-to-treat analysis, morphine reduced objective awake cough frequency by 39·4% (95% CI -54·4 to -19·4; p=0·0005) compared with placebo. Mean daytime cough frequency reduced from 21·6 (SE 1·2) coughs per h at baseline to 12·8 (1·2) coughs per h with morphine, whereas cough rates did not change with placebo (21·5 [SE 1·2] coughs per h to 20·6 [1·2] coughs per h). Overall treatment adherence was 98% in the morphine group and 98% in the placebo group. Adverse events were observed in 17 (40%) of 43 participants in the morphine group and six (14%) of 42 patients in the placebo group. The main side-effects of morphine were nausea (six [14%] of 43 participants) and constipation (nine [21%] of 43). One serious adverse event (death) occurred in the placebo group. In patients with cough related to idiopathic pulmonary fibrosis, low dose controlled-release morphine significantly reduced objective cough counts over 14 days compared with placebo. Morphine shows promise as an effective treatment to palliate cough in patients with idiopathic pulmonary fibrosis, and longer term studies should be the focus of future research. The Jon Moulton Charity Trust.

Influence of the breathing pattern on the pulmonary function of endurance-trained athletes

Proper functioning of the respiratory system is one of the most important determinants of human health. According to current knowledge, the diaphragmatic breathing pattern seems to be the most favourable. However, recent reports indicate that athletes often have dysfunctional breathing patterns, which may be associated with an increased risk of musculoskeletal injuries. The influence of the type of breathing pattern on the mechanical airways in athletes has not been investigated. The aim of the present study was to determine the characteristics and relationships between breathing patterns and respiratory function in athletes. This study included 69 Polish elite endurance athletes (♂40, ♀29) in different sports disciplines and 44 (♂17, ♀27) healthy nonathletes as a control group. All participants underwent pulmonary function tests (spirometry, plethysmography, diffusion capacity for carbon monoxide) with assessment of breathing patterns by the Hi–Lo test. Inspiratory and expiratory resistance (R) and reactance (X) of the respiratory system at a given frequency (5 Hz, 11 Hz, and 19 Hz) were measured by a noninvasive forced oscillation technique. In this study, almost half of the athletes (44.92%) had dysfunctional breathing patterns, although at a lower rate than that in the control group. Diaphragmatic breathing patterns were characterized by higher spirometric, plethysmographic and DLCO values compared to thoracic or abdominal breathing patterns. Similarly, lower inspiratory reactance at 5 Hz (X5%pred.) was observed in the diaphragmatic pattern compared to the thoracic pattern. A diaphragmatic breathing pattern is associated with better pulmonary function test results. However, this study revealed a dysfunctional breathing pattern in almost half of the athletes. These results suggest that the assessment of breathing patterns and the implementation of breathing exercises in athletes are essential to promote proper breathing patterns.

ILD-GAP combined with the monocyte ratio could be a better prognostic prediction model than ILD-GAP in patients with interstitial lung diseases

BackgroundThe ILD-GAP scoring system is known to be useful in predicting prognosis in patients with interstitial lung disease (ILD). An elevated monocyte count was associated with increased risks of IPF poor prognosis. We examined whether the ILD-GAP scoring system combined with the monocyte ratio (ILD-GAPM) is superior to the conventional ILD-GAP model in predicting ILD prognosis.MethodsIn patients with ILD treated between April 2013 and April 2017, we were retrospectively assessed the relationships between baseline clinical parameters, including age, sex, Charlson Comorbidity Index score (CCIS), ILD diagnosis, blood biomarkers, pulmonary function test results, and disease outcomes. In ILD patients were included idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD). We also assessed the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPM models.ResultsA total of 179 patients (mean age, 73 years) were assessed. All of them were taken pulmonary function test, including percentage predicted diffusion capacity for carbon monoxide. ILD patients included 56 IPF cases, 112 iNSIP and CVD-IP cases, 6 CHP cases and 5 UC-ILD cases. ILD-GAPM provided a greater area under the receiver-operating characteristic curve (0.747) than ILD-GAP (0.710) for predicting 3-year ILD-related events. Furthermore, the log-rank test showed that the Kaplan-Meier curves in ILD-GAPM were significantly different by stage (P = 0.015), but not by stage in ILD-GAP (P = 0.074).ConclusionsThe ILD-GAPM model may be a more accurate predictor of prognosis for ILD patients than the ILD-GAP model.

Referral rates and barriers to lung transplantation based on pulmonary function criteria in interstitial lung diseases: a retrospective cohort study.

Interstitial lung diseases (ILD) unresponsive to medical therapy often require lung transplantation (LTx), which prolongs quality of life and survival. Ideal timing for referral for LTx remains challenging, with late referral associated with significant morbidity and mortality. Among other criteria, patients with ILD should be considered for LTx if forced vital capacity (FVC) is less than 80% or diffusion capacity for carbon monoxide (DLCO) is less than 40%. However, data on referral rates are lacking. To evaluate referral rates for LTx based on pulmonary function tests (PFTs) and identify barriers associated with non-referral. A single-center retrospective cohort study. The study consisted of ILD patients who performed PFT between 2014 and 2020. Patients with FVC < 80% or a DLCO < 40% were included in the study. Patients with absolute contraindications to LTx were excluded. Referral rates were computed, and a comparison was made between referred and non-referred subjects. Out of 114 ILD patients meeting criteria for referral to LTx, 35 were referred (30.7%), and 7 proceeded to undergo LTx. Median time from PFT to referral for assessment was 255 days [interquartile range (IQR) 35-1077]. Median time from referral to LTx was 89 days (IQR 59-143). Referred patients were younger (p = 0.003), had lower FVC (p < 0.001), DLCO (p < 0.001), and a higher rate of pulmonary hypertension (p = 0.04). Relatively better PFT, and older age, were significantly associated with non-referral of patients. There is under-referral of ILD patients who are eligible for LTx, which is associated with severe disease and missed opportunities for LTx. Further research is required to validate these findings.

Impact on pulmonary, cardiac, and renal function and long-term quality of life after hospitalization for acute respiratory distress syndrome due to COVID-19: Protocol of the Post-COVID Brazil 3 study.

Evidence about long-term sequelae after hospitalization for acute respiratory distress syndrome due to COVID-19 is still scarce. To evaluate changes in pulmonary, cardiac, and renal function and in quality of life after hospitalization for acute respiratory distress syndrome secondary to COVID-19. This will be a multicenter case-control study of 220 participants. Eligible are patients who are hospitalized for acute respiratory distress syndrome due to COVID-19. In the control group, individuals with no history of hospitalization in the last 12 months or long-term symptoms of COVID-19 will be selected. All individuals will be subjected to pulmonary spirometry with a carbon monoxide diffusion test, chest tomography, cardiac and renal magnetic resonance imaging with gadolinium, ergospirometry, serum and urinary creatinine, total protein, and urinary microalbuminuria, in addition to quality-of-life questionnaires. Patients will be evaluated 12 months after hospital discharge, and controls will be evaluated within 90 days of inclusion in the study. For all the statistical analyses, p < 0.05 is the threshold for significance. The primary outcome of the study will be the pulmonary diffusing capacity for carbon monoxide measured after 12 months. The other parameters of pulmonary, cardiac, and renal function and quality of life are secondary outcomes. This study aims to determine the long-term sequelae of pulmonary, cardiac, and renal function and the quality of life of patients hospitalized for acute respiratory distress syndrome due to COVID-19 in the Brazilian population.

Real-world therapeutic performance of pirfenidone for connective tissue disease-associated interstitial lung diseases.

Pirfenidone (PFD) is commonly applied for antifibrotic treatment in patients with idiopathic pulmonary fibrosis but has rarely been studied in cases with connective tissue disease-associated interstitial lung diseases (CTD-ILDs). We aimed to examine the efficacy of PFD in patients with CTD-ILD based on real-world data. A retrospective cohort study. This study assessed the clinical features of CTD-ILD patients with or without a 6-month PFD treatment. A linear mixed effects model was employed to evaluate the effectiveness of PFD in alleviating lung function changes. Differences in response to PFD were analyzed based on CTD subtype, imaging classification, and pattern of pulmonary function at baseline. A total of 289 patients with CTD-ILD were included, with 155 (53.6%) receiving PFD treatment and the remaining constituting the control group. Patients with the usual interstitial pneumonia (UIP) pattern were more likely to receive PFD treatment, and a relatively lower proportion of cases in the PFD group received immunosuppressive therapies compared to the control group (p < 0.05). At the 6-month follow-up, patients in the PFD group demonstrated a more significant improvement in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) (ΔFVC%: 2.9% vs 0.45%, p = 0.009; ΔDLCO%: 1.9% vs -1.1%, p = 0.004). In the linear mixed model analysis, there was a statistically significant group-time interaction between FVC% and DLCO% changes over time (FVC%: β = 4.52, p < 0.001; DLCO%: β = 4.13, p = 0.003). Furthermore, subgroup analysis indicated that pirfenidone may have superior therapeutic effects in patients with systemic sclerosis (SSc)-associated ILD, non-UIP pattern, and restrictive pattern of lung function at baseline. This study provided real-world data demonstrating the effectiveness of PFD in terms of lung function improvement in patients with CTD-ILD.

A 58-year-old man with progressive dyspnea suffering from Munier-Kuhn syndrome

A 58-year-old man who was a former smoker and had a 20-pack-year smoking history presented to the hospital with worsening shortness of breath. Pulmonary function tests revealed mixed obstructive-restrictive physiology. Forced vital capacity (FVC) was predicted at 68%, forced expiratory volume in 1 second (FEV1) at 60% was predicted, FEV1/FVC at 67% was predicted, and Carbon monoxide (DLCO) diffusion capacity is expected to be 70%. Chest images show increased interstitial density around the hilum. There is massive tracheobronchiomegaly with a tortuous appearance in the airways. There is also a small degree of parenchymal scarring and fibrosis-like reticular perihilar interstitial opacity. CT images show traction bronchiectasis is a finding in the setting of fibrotic lung disease. When lung tissue becomes inelastic due to the formation of dense fibrosis, the airways appear blocked and dilated. Although this patient has dilated airways, the bronchiectasis is greater than the small amount of parenchymal fibrosis seen. Therefore, this process is not caused by parenchymal fibrosis, but rather by inherent pathology of the airway wall. The most frequently reported symptoms of Mounier-Kuhn syndrome are severe cough, difficulty breathing, and recurrent respiratory infections. Patients may complain of chest pain and hemoptysis, but systemic symptoms are rare and require immediate investigation for other diseases. Pulmonary function tests often reveal obstructive pulmonary disease, but in advanced stages there may be limited parenchymal changes, resulting in a mixed appearance, as in a patient's case. Because airway changes are considered irreversible, treatment is aimed at managing symptoms and reducing long-term complications. Recommended lifestyle modifications include quitting smoking and avoiding irritants/particulates. Concurrent COPD or asthma is addressed to limit further morbidity. The infection is treated aggressively, usually requiring broad-spectrum antibiotics to treat atypical infections. The use of expectorants and chest physiotherapy is considered helpful in preventing recurrent infections. Tracheal stenting may be considered if there are specific airways prone to collapse, but the spread of airway involvement limits its potential utility.

Post-COVID changes in lung function 6 months after veno-venous extracorporeal membrane oxygenation: a prospective observational clinical trial.

Severe coronavirus disease 2019 (COVID-19) may require veno-venous extracorporeal membrane oxygenation (V-V ECMO). While V-V ECMO is offered in severe lung injury to COVID-19, long-term respiratory follow-up in these patients is missing. Therefore, we aimed at providing comprehensive data on the long-term respiratory effects of COVID-19 requiring V-V ECMO support during the acute phase of infection. In prospective observational cohort study design, patients with severe COVID-19 receiving invasive mechanical ventilation and V-V ECMO (COVID group, n = 9) and healthy matched controls (n = 9) were evaluated 6 months after hospital discharge. Respiratory system resistance at 5 and 19 Hz (R5, R19), and the area under the reactance curve (AX5) was evaluated using oscillometry characterizing total and central airway resistances, and tissue elasticity, respectively. R5 and R19 difference (R5-R19) reflecting small airway function was also calculated. Forced expired volume in seconds (FEV1), forced expiratory vital capacity (FVC), functional residual capacity (FRC), carbon monoxide diffusion capacity (DLCO) and transfer coefficient (KCO) were measured. The COVID group had a higher AX5 and R5-R19 than the healthy matched control group. However, there was no significant difference in terms of R5 or R19. The COVID group had a lower FEV1 and FVC on spirometry than the healthy matched control group. Further, the COVID group had a lower FRC on plethysmography than the healthy matched control group. Meanwhile, the COVID group had a lower DLCO than healthy matched control group. Nevertheless, its KCO was within the normal range. Severe acute COVID-19 requiring V-V ECMO persistently impairs small airway function and reduces respiratory tissue elasticity, primarily attributed to lung restriction. These findings also suggest that even severe pulmonary pathologies of acute COVID-19 can manifest in a moderate but still persistent lung function impairment 6 months after hospital discharge. NCT05812196.

Deep learning-based prognostication in idiopathic pulmonary fibrosis using chest radiographs.

To develop and validate a deep learning-based prognostic model in patients with idiopathic pulmonary fibrosis (IPF) using chest radiographs. To develop a deep learning-based prognostic model using chest radiographs (DLPM), the patients diagnosed with IPF during 2011-2021 were retrospectively collected and were divided into training (n = 1007), validation (n = 117), and internal test (n = 187) datasets. Up to 10 consecutive radiographs were included for each patient. For external testing, three cohorts from independent institutions were collected (n = 152, 141, and 207). The discrimination performance of DLPM was evaluated using areas under the time-dependent receiver operating characteristic curves (TD-AUCs) for 3-year survival and compared with that of forced vital capacity (FVC). Multivariable Cox regression was performed to investigate whether the DLPM was an independent prognostic factor from FVC. We devised a modified gender-age-physiology (GAP) index (GAP-CR), by replacing DLCO with DLPM. DLPM showed similar-to-higher performance at predicting 3-year survival than FVC in three external test cohorts (TD-AUC: 0.83 [95% CI: 0.76-0.90] vs. 0.68 [0.59-0.77], p < 0.001; 0.76 [0.68-0.85] vs. 0.70 [0.60-0.80], p = 0.21; 0.79 [0.72-0.86] vs. 0.76 [0.69-0.83], p = 0.41). DLPM worked as an independent prognostic factor from FVC in all three cohorts (ps < 0.001). The GAP-CR index showed a higher 3-year TD-AUC than the original GAP index in two of the three external test cohorts (TD-AUC: 0.85 [0.80-0.91] vs. 0.79 [0.72-0.86], p = 0.02; 0.72 [0.64-0.80] vs. 0.69 [0.61-0.78], p = 0.56; 0.76 [0.69-0.83] vs. 0.68 [0.60-0.76], p = 0.01). A deep learning model successfully predicted survival in patients with IPF from chest radiographs, comparable to and independent of FVC. Deep learning-based prognostication from chest radiographs offers comparable-to-higher prognostic performance than forced vital capacity. •A deep learning-based prognostic model for idiopathic pulmonary fibrosis was developed using 6063 radiographs. •The prognostic performance of the model was comparable-to-higher than forced vital capacity, and was independent from FVC in all three external test cohorts. •A modified gender-age-physiology index replacing diffusing capacity for carbon monoxide with the deep learning model showed higher performance than the original index in two external test cohorts.