Decline In Forced Vital Capacity Research Articles

The phenotype of mixed connective tissue disease patients having associated interstitial lung disease

ObjectiveWe aimed to compare two matched populations of patients with MTCD with and without associated ILD and to identify predictive factors for ILD progression and severity. MethodsThis international multicenter retrospective study (14 tertiary hospitals), included MCTD patients who fulfilled at least one historical MCTD classification criteria. ILD was defined by the presence of typical chest high-resolution computed tomography (HRCT) abnormalities. Factors associated with ILD were assessed at baseline. Long-term progressive ILD was assessed in MCTD-ILD patients with multiple forced vital capacity (FVC) measurements. Results300 patients with MCTD were included. Mean age at diagnosis was 39.7 ± 15.4 years and 191 (63.7%) were women. Mean follow-up was 7.8 ± 5.5 years. At baseline, we identified several factors associated with ILD presence: older age (p = 0.01), skin thickening (p = 0.03), upper gastro-intestinal (GI) symptoms (p<0.001), FVC <80% (p<0.0001), diffusing capacity for carbon monoxide <80% (p<0.0001), anti-topoisomerase antibodies (p = 0.01), SSA/Ro antibodies (p = 0.02), cryoglobulinemia (p = 0.04) and elevated C-reactive protein (p<0.001). Patients with MTCD-ILD were more likely to be treated with synthetic immunosuppressant agents (p<0.001) in particular mycophenolate mofetil (p = 0.03). Digital ulcers (DU) were identified as a risk factor for FVC decline >10%. During follow-up mortality was higher in the MTCD-ILD group (p<0.001). ConclusionIn this large international cohort of patients with MTCD, we identified different factors associated with ILD. Our findings also provide evidence that MCTD-ILD patients have increased mortality and that DU are associated with progressive lung disease.

Lung function trajectories in patients with idiopathic pulmonary fibrosis

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF.MethodsPatients with IPF that was diagnosed or confirmed at the enrolling centre in the previous 6 months were enrolled into the IPF-PRO Registry between June 2014 and October 2018. Patients were followed prospectively, with lung function data collected as part of routine clinical care. Mean trajectories of FVC and DLco % predicted in all patients and in subgroups by characteristics assessed at enrolment were estimated using a joint model that accounted for factors such as disease severity and visit patterns.ResultsOf 1002 patients in the registry, 941 had ≥ 1 FVC and/or DLco measurement after enrolment. The median (Q1, Q3) follow-up period was 35.1 (18.9, 47.2) months. Overall, mean estimated declines in FVC and DLco % predicted were 2.8% and 2.9% per year, respectively. There was no evidence that the mean trajectories of FVC or DLco had a non-linear relationship with time at the population level. Patients who were male, white, had a family history of ILD, were using oxygen, or had prior/current use of antifibrotic therapy at enrolment had greater rates of decline in FVC % predicted. Patients who were male or white had greater rates of decline in DLco % predicted.ConclusionsData from the IPF-PRO Registry suggest a constant rate of decline in lung function over a prolonged period, supporting the inexorably progressive nature of IPF. A graphical abstract summarising the data in this manuscript is available at: https://www.usscicomms.com/respiratory/IPF-PRORegistry_LungFunctionTrajectories.Trial registrationNCT01915511.

Interaction of sex and onset site on the disease trajectory of amyotrophic lateral sclerosis.

Studies showed the impact of sex and onset site (spinal or bulbar) on disease onset and survival in ALS. However, they mainly result from cross-sectional or survival analysis, and the interaction of sex and onset site on the different proxies of disease trajectory has not been fully investigated. We selected all patients with repeated observations in the PRO-ACT database. We divided them into four groups depending on their sex and onset site. We estimated a multivariate disease progression model, named ALS Course Map, to investigate the combined temporal changes of the four sub-scores of the revised ALS functional rating scale (ALSFRSr), the forced vital capacity (FVC), and the body mass index (BMI). We then compared the progression rate, the estimated age at onset, and the relative progression of the outcomes across each group. We included 1438 patients from the PRO-ACT database. They were 51% men with spinal onset, 12% men with bulbar onset, 26% women with spinal onset, and 11% women with bulbar onset. We showed a significant influence of both sex and onset site on the ALSFRSr progression. The BMI decreased 8.9 months earlier (95% CI [3.9, 13.8]) in women than men, after correction for the onset site. Among patients with bulbar onset, FVC was impaired 2.6 months earlier (95% CI [0.6, 4.6]) in women. Using a multivariable disease modelling approach, we showed that sex and onset site are important drivers of the progression of motor function, BMI, and FVC decline.

Interstitial lung disease in patients with systemic sclerosis: what can we learn from the SENSCIS trial?

The SENSCIS trial of nintedanib versus placebo is the largest trial conducted to date in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). This trial enrolled 576 patients with an extent of fibrotic ILD on high-resolution computed tomography of >10%. Median time since first non-Raynaud symptom was 3.4 years. Almost half of the patients were receiving a stable dose of mycophenolate at baseline. Key findings of the trial included that at baseline, despite having significant lung fibrosis on HRCT and impairment in lung function, 20% of the patients did not have cough and 30% did not have dyspnoea. Over 52 weeks, a marked decline in forced vital capacity (FVC) was observed (-112.0 mL/year in patients with diffuse cutaneous SSc [dcSSc] and -74.5 mL/year in patients with limited cutaneous SSc [lcSSc] in the placebo group). Loss of FVC was associated with an increased risk of SSc-related hospitalisation or death. Although certain subgroups of patients were at higher risk of progression, it was not possible to make a robust prediction of FVC decline based on baseline characteristics. The relative effect of nintedanib versus placebo on reducing the rate of FVC decline was consistent across subgroups based on factors including anti-topoisomerase I antibody (ATA) status, dcSSc vs. lcSSc, and use of mycophenolate at baseline. The side-effects of nintedanib were mainly gastrointestinal events, particularly diarrhoea. Nintedanib did not have a significant effect on skin fibrosis or health-related quality of life. Overall, the results of the SENSCIS trial support the importance of prompt identification and treatment of SSc-ILD and the consideration of nintedanib as a treatment option.

Nintedanib administration after the onset of acute exacerbation of interstitial lung disease in the real world

Nintedanib reduces the decline in forced vital capacity and extends the time to the first acute exacerbation of interstitial lung disease (AE-ILD). However, the effect of additional nintedanib administration after AE-ILD onset is unknown. This study aimed to investigate the efficacy and safety of nintedanib administration after AE-ILD development. We retrospectively collected the data of 33 patients who developed AE-ILD between April 2014 and January 2022. Eleven patients who received nintedanib after AE-ILD development and the remaining who did not were classified into the N and No-N groups, respectively. The survival time in the N group tended to be longer than that in the No-N group. The generalized Wilcoxson test revealed that the cumulative mortality at 90 days from AE-ILD onset was significantly lower in the N group. The time to subsequent AE-ILD development was significantly longer in the N group than that in the No-N group. The incidence of adverse gastrointestinal effects and liver dysfunction in the N group was 9–18%. Treatment without nintedanib after AE-ILD development and the ratio of arterial oxygen partial pressure to fractional inspired oxygen were significant independent prognostic factors in the multivariate analysis. Thus, nintedanib administration may be a treatment option for AE-ILD.

Design of a phase III, double-blind, randomised, placebo-controlled trial of BI 1015550 in patients with idiopathic pulmonary fibrosis (FIBRONEER-IPF)

IntroductionThere is an unmet need for new treatments for idiopathic pulmonary fibrosis (IPF). The oral preferential phosphodiesterase 4B inhibitor, BI 1015550, prevented a decline in forced vital capacity (FVC) in...

Lung volumes differentiate the predominance of emphysema versus airway disease phenotype in early COPD: an observational study of the COPDGene cohort.

Lung volumes identify the "susceptible smokers" who progress to develop spirometric COPD. However, among susceptible smokers, development of spirometric COPD seems to be heterogeneous, suggesting the presence of different pathological mechanisms during early establishment of spirometric COPD. The objective of the present study was to determine the differential patterns of radiographic pathologies among susceptible smokers. We categorised smokers with preserved spirometry (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0) in the Genetic Epidemiology of COPD (COPDGene) cohort based on tertiles (low, intermediate and high) of lung volumes (either total lung capacity (TLC), functional residual capacity FRC or FRC/TLC) at baseline visit. We then examined the differential patterns of change in spirometry and the associated prevalence of computed tomography measured pathologies of emphysema and airway disease with those categories of lung volumes. The pattern of spirometric change differed when participants were categorised by TLC versus FRC/TLC: those in the high TLC tertile showed stable forced expiratory volume in 1 s (FEV1), but enlarging forced vital capacity (FVC), while those in the high FRC/TLC tertile showed decline in both FEV1 and FVC. When participants from the high TLC and high FRC/TLC tertiles were partitioned into mutually exclusive groups, compared to those with high TLC, those with high FRC/TLC had lesser emphysema, but greater air trapping, more self-reported respiratory symptoms and exacerbation episodes and higher likelihood of progressing to more severe spirometric disease (GOLD stages 2-4 versus GOLD stage 1). Lung volumes identify distinct physiological and radiographic phenotypes in early disease among susceptible smokers and predict the rate of spirometric disease progression and the severity of symptoms in early COPD.

The Presence of T Allele (rs35705950) of the MUC5B Gene Predicts Lower Baseline Forced Vital Capacity and Its Subsequent Decline in Patients with Hypersensitivity Pneumonitis.

Hypersensitivity pneumonitis (HP) is an exposure-related interstitial lung disease with two phenotypes-fibrotic and non-fibrotic. Genetic predisposition is an important factor in the disease pathogenesis and fibrosis development. Several genes are supposed to be associated with the fibrosing cascade in the lungs. One of the best-recognized and most prevalent is the common MUC5B gene promoter region polymorphism variant rs35705950. The aim of our study was to establish the frequency of the minor allele of the MUC5B gene in the population of patients with HP and to find the relationship between the MUC5B promoter region polymorphism and the development of lung fibrosis, the severity of the disease course, and the response to the treatment in patients with HP. Eighty-six consecutive patients with HP were tested for the genetic variant rs35705950 of the MUC-5B gene. Demographic, radiological, and functional parameters were collected. The relationship between the presence of the T allele and lung fibrosis, pulmonary function test parameters, and the treatment response were analyzed. The minor allele frequency in the study group was 17%, with the distribution of the genotypes GG in 69.8% of subjects and GT/TT in 30.2%. Patients with the GT/TT phenotype had significantly lower baseline forced vital capacity (FVC) and significantly more frequently had a decline in FVC with time. The prevalence of lung fibrosis in high-resolution computed tomography (HRCT) was not significantly increased in GT/TT variant carriers compared to GG ones. The patients with the T allele tended to respond worse to immunomodulatory treatment and more frequently received antifibrotic drugs. In conclusions: The frequency of MUC5B polymorphism in HP patients is high. The T allele may indicate a worse disease course, worse immunomodulatory treatment response, and earlier need for antifibrotic treatment.

Emphysema and interstitial lung disease in systemic sclerosis-related pulmonary hypertension

Pulmonary hypertension (PH) is a major cause of morbidity and mortality among patients with systemic sclerosis (SSc) [ [1] Steen V.D. Medsger T.A. Changes in causes of death in systemic sclerosis, 1972-2002. Ann. Rheum. Dis. 2007 Feb 2; 66 (PMCID: PMC1955114): 940-944 Crossref PubMed Scopus (1174) Google Scholar ]. Patients with SSc-PH and concomitant interstitial lung disease (ILD) have worse clinical outcomes compared to those with SSc-PH, alone [ 2 Chauvelot L. Gamondes D. Berthiller J. Nieves A. Renard S. Catella-Chatron J. Ahmad K. Bertoletti L. Camara B. Gomez E. Launay D. Montani D. Mornex J.F. Prévot G. Sanchez O. Schott A.M. Subtil F. Traclet J. Turquier S. Zeghmar S. Habib G. Reynaud-Gaubert M. Humbert M. Cottin V. Hemodynamic response to treatment and outcomes in pulmonary hypertension associated with interstitial lung disease versus pulmonary arterial hypertension in systemic sclerosis: data from a study identifying prognostic factors in pulmonary hypertension associated with interstitial lung disease. Arthritis Rheumatol Hoboken NJ. 2021 Feb; 73 (PMID: 32892515): 295-304 Google Scholar , 3 Le Pavec J. Girgis R.E. Lechtzin N. Mathai S.C. Launay D. Hummers L.K. Zaiman A. Sitbon O. Simonneau G. Humbert M. Hassoun P.M. Systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease: impact of pulmonary arterial hypertension therapies. Arthritis Rheum. 2011 Aug; 63 (PMID: 21538327): 2456-2464 Crossref PubMed Scopus (102) Google Scholar , 4 Mathai S.C. Hummers L.K. Champion H.C. Wigley F.M. Zaiman A. Hassoun P.M. Girgis R.E. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum. 2009 Feb; 60 (PMID: 19180517): 569-577 Crossref PubMed Scopus (208) Google Scholar ]. In patients with increasing ILD severity, as assessed by forced vital capacity (FVC), there is a trend toward increased all-cause mortality [ [5] Sangani R.A. Lui J.K. Gillmeyer K.R. Trojanowski M.A. Bujor A.M. LaValley M.P. Klings E.S. Clinical Characteristics and outcomes in pulmonary manifestations of systemic sclerosis: contribution from pulmonary hypertension and interstitial lung disease severity. Pulm. Circ. 2022 Jul 16; (pul2.12117) Crossref Scopus (0) Google Scholar ]. Common in restrictive lung diseases including ILD [ [5] Sangani R.A. Lui J.K. Gillmeyer K.R. Trojanowski M.A. Bujor A.M. LaValley M.P. Klings E.S. Clinical Characteristics and outcomes in pulmonary manifestations of systemic sclerosis: contribution from pulmonary hypertension and interstitial lung disease severity. Pulm. Circ. 2022 Jul 16; (pul2.12117) Crossref Scopus (0) Google Scholar ], reduced FVC also occur in obstructive lung diseases, including chronic obstructive pulmonary disease (COPD), which can also affect SSc patients. To date, little is known about the impact of concurrent obstructive lung disease in SSc-PH which may both confound FVC on pulmonary function testing (PFT) used as a marker for ILD severity [ [5] Sangani R.A. Lui J.K. Gillmeyer K.R. Trojanowski M.A. Bujor A.M. LaValley M.P. Klings E.S. Clinical Characteristics and outcomes in pulmonary manifestations of systemic sclerosis: contribution from pulmonary hypertension and interstitial lung disease severity. Pulm. Circ. 2022 Jul 16; (pul2.12117) Crossref Scopus (0) Google Scholar ], and its contribution to overall mortality [ [6] Koo B.S. Park K.Y. Lee H.J. Kim H.J. Ahn H.S. Yim S.Y. Jun J.B. Effect of combined pulmonary fibrosis and emphysema on patients with connective tissue diseases and systemic sclerosis: a systematic review and meta-analysis. Arthritis Res. Ther. 2021 Apr 6; 23 (PMCID: PMC8022385): 100 Crossref Scopus (4) Google Scholar , [7] Ariani A. Silva M. Bravi E. Parisi S. Saracco M. De Gennaro F. Caimmi C. Girelli F. De Santis M. Volpe A. Lumetti F. Hax V. Bredemeier M. Alfieri V. Santilli D. Bodini F.C. Lucchini G. Mozzani F. Seletti V. Bacchini E. Arrigoni E. Giuggioli D. Chakr R. Idolazzi L. Bertorelli G. Imberti D. Michieletti E. Paolazzi G. Fusaro E. Chetta A.A. Scirè C.A. Sverzellati N. Overall mortality in combined pulmonary fibrosis and emphysema related to systemic sclerosis. RMD Open. 2019; 5 (PMCID: PMC6397433)e000820 Crossref Scopus (14) Google Scholar ]. Our goal in this study was to characterize the impact of FVC on clinical outcomes in SSc-PH when adjusted for radiologic ILD/emphysema. We hypothesized that FVC decline in any hypoxic lung disease, regardless of etiology, was associated with increased transplant-free, all-cause mortality in SSc-PH.

Residential greenspace and lung function decline over 20 years in a prospective cohort: The ECRHS study

BackgroundThe few studies that have examined associations between greenspace and lung function in adulthood have yielded conflicting results and none have examined whether the rate of lung function decline is affected. ObjectiveWe explored the association between residential greenspace and change in lung function over 20 years in 5559 adults from 22 centers in 11 countries participating in the population-based, international European Community Respiratory Health Survey. MethodsForced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry when participants were approximately 35 (1990–1994), 44 (1999–2003), and 55 (2010–2014) years old. Greenness was assessed as the mean Normalized Difference Vegetation Index (NDVI) in 500 m, 300 m, and 100 m circular buffers around the residential addresses at the time of lung function measurement. Green spaces were defined as the presence of agricultural, natural, or urban green spaces in a circular 300 m buffer. Associations of these greenspace parameters with the rate of lung function change were assessed using adjusted linear mixed effects regression models with random intercepts for subjects nested within centers. Sensitivity analyses considered air pollution exposures. ResultsA 0.2-increase (average interquartile range) in NDVI in the 500 m buffer was consistently associated with a faster decline in FVC (−1.25 mL/year [95% confidence interval: −2.18 to −0.33]). These associations were especially pronounced in females and those living in areas with low PM10 levels. We found no consistent associations with FEV1 and the FEV1/FVC ratio. Residing near forests or urban green spaces was associated with a faster decline in FEV1, while agricultural land and forests were related to a greater decline in FVC. ConclusionsMore residential greenspace was not associated with better lung function in middle-aged European adults. Instead, we observed slight but consistent declines in lung function parameters. The potentially detrimental association requires verification in future studies.

Lung Function Decline in Young Adulthood and Coronary Artery Calcium Progression in Midlife

BackgroundReduced lung function has been linked to cardiovascular disease, but population-based evidence on the relationship between lung function decline and coronary artery calcium (CAC) progression is rare. MethodsA total of 2694 participants (44.7% men) with a mean ± standard deviation age of 40.4 ± 3.6 years from the Coronary Artery Risk Development in Young Adults (CARDIA) were included. The rates of decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) over a 20-year period were calculated for each participant and categorized into quartiles. The primary outcome was CAC progression. ResultsDuring a mean follow-up of 8.9 years, 455 (16.9%) participants had CAC progression. After adjusting for traditional cardiovascular risk factors, the hazard ratios (95% confidence intervals [CIs]) for CAC progression were higher for participants in the 2nd (Q2), 3rd (Q3), and highest quartiles (Q4) of FVC decline compared with those in the lowest quartile (Q1): 1.366 (1.003-1.861), 1.412 (1.035-1.927), and 1.789 (1.318-2.428), respectively. Similar trends were observed for the association between FEV1 and CAC progression. The association remained robust across a series of sensitivity analyses and all subgroups. ConclusionsA faster decline in FVC or FEV1 during young adulthood is independently associated with an increased risk of CAC progression in midlife. Maintaining optimal lung function during young adulthood may improve future cardiovascular health.

Diagnostic finding on high-resolution computed tomography (HRCT) predicts a good response to pirfenidone in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a debilitating condition, with a life expectancy of 2 to 5 years after diagnosis. Pirfenidone is a drug that has been shown to reduce the decline in forced vital capacity (FVC). We sought to identify whether different patterns on high-resolution computed tomography (HRCT) have different clinical effects through a retrospective comparison of baseline values and changes in pulmonary function tests (PFTs) after treatment with pirfenidone. We retrospectively analyzed data from IPF patients treated with pirfenidone at Nanjing Drum Tower Hospital in Jiangsu Province, China. According to the HRCT pattern, the patients were divided into usual interstitial pneumonitis (UIP) and possible UIP groups. Baseline clinical characteristics and changes every 6 months in the PFTs during the follow-up period were compared between the 2 groups. A total of 65 consecutive patients were enrolled. According to the HRCT pattern, patients were clustered into the UIP group (n = 46) and possible UIP group (n = 19). No difference was observed in the baseline PFTs ratio between the 2 groups. The FVC values of the 2 groups were not significantly different at the initial treatment and at 6 and 12 months after pirfenidone treatment (P = .081, 0.099, and 0.236, respectively). The improvement in % diffusion capacity of the lung for carbon monoxide (%DLCO) was higher in the possible UIP group after 6 and 12 months of pirfenidone treatment (P = .149, 0.026, and 0.025, respectively). The annual decrease in FVC was not significantly different between the 2 groups, and the annual decrease in %DLCO in the UIP group was significantly higher than that in patients with the possible UIP type (-7.767 ± 12.797 vs 0.342 ± 20.358, P < .05). These results indicate that patients with IPF with a possible UIP pattern on HRCT showed indications of a good response to pirfenidone.

The Efficacy and Safety of Rituximab in Patients with Idiopathic Inflammatory Myopathy-Associated Interstitial Lung Disease: Case Series.

Idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD) is often rapidly progressive with a poor prognosis; however, no standard therapeutic regimen has been identified. This study aimed to investigate the efficacy and safety of rituximab in IIM-ILD patients. Five patients who had been administered rituximab for IIM-ILD at least once between August 2016 and November 2021 were included. Lung function decline was compared one year before and after rituximab. Disease progression, defined as a greater than 10% relative decline in forced vital capacity (FVC) compared to the baseline, was also compared before and after treatment. Adverse events were recorded for safety analysis. Five IIM-ILD patients received eight cycles. FVC-predicted values significantly decreased from 6 months before rituximab administration to those at the baseline (54.1% predicted (pre-6 months) vs. 48.5% predicted (baseline), p = 0.043); however, the FVC decline stabilized after rituximab. The rate of disease progression before rituximab showed a tendency to decrease after rituximab (75% (before) vs. 12.5% (6 months after, p = 0.059) vs. 14.3% (12 months after, p = 0.102)). Three adverse events developed, but none resulted in death. Rituximab can stabilize lung function decline with tolerable safety in Korean IIM patients with refractory ILD.

The effect of nintedanib on lung functions and survival in idiopathic pulmonary fibrosis: real-life analysis of the Czech EMPIRE registry

IntroductionThe antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry.Patients/methodsData of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed. The influence of nintedanib on overall survival (OS), pulmonary function parameters as forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO), as well as GAP score (gender, age, physiology) and and CPI (composite physiological index) were investigated.ResultsDuring 2 year follow-up we observed that nintedanib treated patients had longer OS, compared to those treated with no-antifibrotic drugs (p < 0.00001). Nintedanib reduces risk of mortality over no-antifibrotic treatment by 55% (p < 0.001). We have observed no significant difference in the rate of FVC and DLCO decline between the NIN and NAF group. Changes within 24 months from baseline in CPI were not significant between the groups (NAF and NIN).ConclusionOur real-practice study showed the benefit of nintedanib treatment on survival. There were no significant differences between NIN and NAF groups in changes from baseline in FVC %, DLCO % predicted and CPI.

Treatment of rheumatoid arthritis-associated interstitial lung disease in a multi-center registry cohort.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is challenging to manage, with a paucity of robust data to guide treatment. Our aim was to characterize the pharmacologic treatment of RA-ILD utilizing a retrospective design in a national multi-center prospective cohort, and to identify associations between treatment and change in lung function and survival. Patients with RA-ILD and a radiological pattern of non-specific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) were included. Unadjusted and adjusted linear mixed models and Cox proportional hazards models were used to compare lung function change and risk of death or lung transplant by radiologic patterns and treatment. Of 161 patients with RA-ILD, UIP pattern was more common than NSIP (55.9% vs. 44.1%). Only 44/161 (27%) patients were treated over median follow-up of 4 years with medication choice appearing unrelated to patient-specific variables. Decline in forced vital capacity (FVC) was not associated with treatment. Patients with NSIP had lower risk of death or transplant, compared to UIP (P=0.0042). In patients with NSIP, there was no difference in time to death or transplant comparing treated to untreated in adjusted models [hazard ratio (HR) =0.73; 95% confidence interval (CI): 0.15-3.62; P=0.70]. Similarly, in patients with UIP, there was no difference in time to death or lung transplant between treated and untreated in adjusted models (HR =1.06; 95% CI: 0.49-2.28; P=0.89). Treatment of RA-ILD is heterogeneous, with most patients in this cohort not receiving treatment. Patients with UIP had worse outcomes compared to NSIP, similar to other cohorts. Randomized clinical trials are needed to inform pharmacologic therapy in this patient population.

Metabolically healthy and unhealthy obesity and the development of lung dysfunction

We investigated the association of metabolically healthy (MH) and unhealthy (MU) obesity with incident lung dysfunction. This cohort study included 253,698 Korean lung disease-free adults (mean age, 37.4 years) at baseline. Spirometry-defined lung dysfunction was classified as a restrictive pattern (RP) or obstructive pattern (OP). We defined obesity as BMI ≥ 25 kg/m2 and MH as the absence of any metabolic syndrome components with a homeostasis model assessment of insulin resistance < 2.5: otherwise, participants were considered MU. During a median follow-up of 4.9 years, 10,775 RP cases and 7140 OP cases develped. Both MH and MU obesity showed a positive association with incident RP, with a stronger association in the MU than in the MH group (Pinteraction = 0.001). Multivariable-adjusted hazard ratios (95% CI) for incident RP comparing obesity to the normal-weight category was 1.15 (1.05–1.25) among the MH group and 1.38 (1.30–1.47) among MU group. Conversely, obesity was inversely associated with OP because of a greater decline in forced vital capacity than forced expiratory volume in 1 s. Both MH and MU obesity were positively associated with RP. However, the associations between obesity, metabolic health, and lung functions might vary depending on the type of lung disease.

Eligibility criteria from pharmaceutical randomised controlled trials of idiopathic pulmonary fibrosis: a registry-based study.

Little is known about generalisability of randomised controlled trials (RCTs) for idiopathic pulmonary fibrosis (IPF). We evaluated eligibility criteria for phase III IPF RCTs to determine their representativeness in clinical registries, and calculated forced vital capacity (FVC) changes according to eligibility criteria. Common eligibility criteria used in >60% of IPF RCTs were identified from a literature search and applied to patients with IPF from prospective Australian and Canadian registries. Additional pre-specified criteria of 6-min walk distance (6MWD) and different measures of preceding disease progression were also evaluated. Joint longitudinal-survival modelling was used to compare FVC decline according to eligibility for individual and composite criteria. Out of 990 patients with IPF, 527 (53%) met all common RCT eligibility criteria at the first clinic visit, including 343 with definite IPF and 184 with radiological probable usual interstitial pneumonia pattern without histological confirmation (i.e. provisional IPF). The percentages of eligible patients for landmark RCTs of nintedanib and pirfenidone were 19-50%. Adding 6MWD ≥150 m and different measures of preceding disease progression to the composite common criteria reduced the percentages of patients meeting eligibility to 52% (n=516) and 4-18% (n=12-61), respectively. Patients meeting the composite common criteria had less-rapid 1-year FVC decline than those who did not (-90 versus -103 mL, p=0.01). Definite IPF generally had more-rapid 1-year FVC decline compared to provisional IPF. Eligibility criteria of previous IPF RCTs have limited generalisability to clinical IPF populations, with FVC decline differing between eligible and ineligible populations.

Evaluation of Lung Functions, Blood Pressure, and Hearing Deterioration in Tile Setters.

Tile setters in construction industries are exposed to a potent risk of silicosis as they are constantly exposed to crystalline silica dust during concrete finishing, cutting and fixing of the ceramic tiles. The noise produced by instruments used in tile settings may lead to noise-induced hearing loss. Noise above the permissible limit of 85 dB may lead to autonomic changes and alteration in blood pressure. These facts gave us an impetus to evaluate the pulmonary functions, blood pressure and hearing deterioration in tile setters and correlate these parameters for their present functional status with duration of exposure to tile cutting profession. The pulmonary functions were evaluated with spirometer, autonomic status by recording the blood pressure and hearing loss by calculating the Hearing Deterioration Index (HDI) for hearing loss. There was significant decline in forced vital capacity (FVC), forced expiratory volume 1 sec (FEV1) and forced expiratory volume 1% (FEV1%) in tile setters. The decline in FVC, FEV1 and FEV1% was significantly higher in subjects with exposure of more than five years. There was increased systolic and diastolic blood pressure in those having more than five years of exposure in the tile setting profession as compared to less than five years. There was a positive correlationbetween years of service in the tile setting profession as well as sound exposure level with HDI and blood pressure in our subjects. Prolonged exposure to the tile setting profession may lead to compromised lung function, hypertension and hearing deterioration in tile setters.

Correlation of monocyte counts with clinical outcomes in idiopathic nonspecific interstitial pneumonia

Higher blood monocyte counts are related to worse survival in idiopathic pulmonary fibrosis. However, studies evaluating the association between blood monocyte counts and clinical outcomes of idiopathic nonspecific interstitial pneumonia (iNSIP) are lacking. We evaluated the impact of monocyte counts on iNSIP prognosis. iNSIP patients (n = 126; median age, 60 years; female, n = 64 [50.8%]) diagnosed by surgical lung biopsy were enrolled and categorized into low (monocyte < 600/µL) and high (monocyte ≥ 600/µL) monocyte groups. The median follow-up duration was 53.0 months. After adjusting for age, sex, and smoking history, the annual decline in forced vital capacity (FVC) showed differences between the monocyte groups (Pinteraction = 0.006) (low vs. high; − 28.49 mL/year vs. − 65.76 mL/year). The high-monocyte group showed a worse survival rate (P = 0.01) compared to low monocyte group. The 5-year survival rates were 83% and 72% in the low- and high-monocyte groups, respectively. In the Cox-proportional hazard analysis, older age, male sex, low baseline FVC, and diffusing capacity of the lung for carbon monoxide were independent risk factors for mortality. However, monocyte count (Hazard ratio 1.61, P = 0.126) was not an independent prognostic factor. Although high monocyte count might be associated with faster lung function decline, it could not independently predict survival in iNSIP.

Prognostic Significance of Obstructive Sleep Apnea in a Population of Subjects with Interstitial Lung Diseases.

Obstructive sleep apnea (OSA) is often observed in subjects with interstitial lung disease (ILD). It may have a negative impact on the course of ILD, but its prognostic significance in relation to other known indicators of poor outcome is unclear. After a detailed work-up, including overnight unattended type III polygraphy, all subjects newly diagnosed with ILDs referred to our clinics were followed-up for at least 1.5years or until death or progression of disease [> 10% decline in forced vital capacity (FVC) below baseline]. We analyzed relationships between some prespecified variables of interest, including sleeping results, to establish parameters predictive of progressive course. Our population consisted of 46 subjects (mean age 59.6years; males 61%); 23.9% and 41% had idiopathic pulmonary fibrosis and ILD associated with systemic diseases, respectively. Mean baseline forced vital capacity and diffusion capacity of carbon monoxide were 83% and 57% of predicted, respectively. Mean (± SE) Apnea-Hypopnea Index (AHI) was 17 (± 3) events/h. AHI in the ranges 5-14.9, 15-29.9, and ≥ 30 was recorded in 14 (31%), 6 (13%), and 9 (20%) subjects, respectively. Mean distance covered in the 6-MWG walk test (6MWT) was 302 (± 19) m and 26 subjects (57%) showed exertional oxyhemoglobin desaturation. The median follow-up was about 18months. Multivariate logistic regression analysis showed that exertional desaturation (HR 8.2; 1.8-36.5 95% CI; p = 0.006) and AHI ≥ 30, namely the threshold of severe OSA (HR 7.5; 1.8-30.6; p = 0.005), were the only independent variables related to progressive disease course. We conclude that exertional desaturation and elevated AHI had independent negative prognostic significance in our ILD population.