Forced Vital Capacity In Patients Research Articles

Respiratory function in adult patients with spinal muscular atrophy treated with nusinersen - a monocenter observational study.

Insufficiency of respiratory muscles is the most important reason for mortality in the natural history of SMA. Thus, improvement or stabilization of respiratory function by disease-modifying therapies (DMT) is a very important issue. We examined respiratory function using forced vital capacity (FVC) in 42 adult SMA patients (2 SMA type 1, 15 SMA type 2, 24 SMA type 3, 1 SMA type 4, median age 37 years, range 17-61 years) treated with nusinersen for a median of 22.1 months (range 2.1 to 46.7 months). Change in FVC was assessed using mixed effects linear regression models. Baseline FVC differed significantly between SMA type 1 (4.0, 8.0%), 2 (median 22.0%, IQR 18.0-44.0), 3 (median 81.0%, IQR 67.0-90.8) and, respectively, type 4 (84.0%) patients reflecting the heterogeneity of respiratory impairment based on the SMA type in adulthood (p < 0.0001). FVC remained stable during follow-up (mean -0.047, 95% CI -0.115 to 0.020, p = 0.17); however, subgroup analysis showed an increase in FVC of type 2 patients (mean 0.144, 95% CI 0.086 to 0.202, p < 0.0001) and a decrease in FVC of type 3/4 patients (-0.142, 95% CI -0.239 to -0.044, p = 0.005). The observed improvement in FVC in patients with SMA type 2 can be seen as a therapeutic response differing from the progressive decline typically seen in the spontaneous course. For SMA type 3/4 patients approaching normal spirometry at baseline, FVC may only be of limited use as an outcome parameter due to ceiling effects.

Systemic corticosteroids in fibrotic lung disease: a systematic review and meta-analysis

ObjectivesWe aimed to assess the available evidence for corticosteroids in fibrotic interstitial lung disease (fILD) to inform the randomised embedded multifactorial adaptive platform ILD.DesignSystematic review and meta-analysis.Data sourcesWe searched Embase,...

Disease progression and changes in KL-6 in patients with limited cutaneous systemic sclerosis-associated interstitial lung disease

BackgroundLittle is known about the annual change in Krebs von Lungen-6 (KL-6) and its correlation with forced vital capacity (FVC) in limited cutaneous systemic sclerosis-associated interstitial lung disease (lcSSc-ILD). We aimed to clarify the correlation during the clinical course. MethodsWe retrospectively reviewed data from consecutive patients with lcSSc-ILD. We measured FVC and KL-6 annually and calculated their annual changes using the difference in absolute values. Decline in FVC was defined as annual decline in FVC ≥5 %. ResultsThirty-eight patients with SSc-ILD were included. The median age was 62 years and 58 % were female. The median FVC was 87.3 % and the median KL-6 was 1629 U/ml. The median observation period was 55.2 months and the annual changes in FVC and KL-6 were evaluated 151 times simultaneously. The annual change in KL-6 had a significant negative correlation with that in FVC in the first year from the initial evaluation (from the baseline to one-year follow-up) (r = −0.819, p < 0.01), but not after the first year. In the multivariable analysis adjusted by age, sex, and FVC at each year, the annual change of KL-6 (per 100 U/ml) was significantly associated with decline in FVC in the first year (odds ratio: 3.03, 95 % confidence interval: 1.21–7.59, p = 0.02), but not after the first year. ConclusionsOnly in the first year from the initial evaluation, there was negative correlation between the annual change in FVC and that in KL-6 and the annual elevation in KL-6 was associated with decline in FVC in patients with lcSSc-ILD.

Real-World Clinical Efficacy of Antifibrotic Agents for Idiopathic Pulmonary Fibrosis: A Single-Center Retrospective Study in Japan.

The antifibrotic drugs, nintedanib and pirfenidone, inhibit the decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF). Nintedanib also inhibits the onset of acute exacerbation and reduces the risk of all-cause mortality. However, their effectiveness in real-world practice remains unclear. Our study aimed to investigate the changes in forced vital capacity, survival period, causes of death, and risk factors for mortality in patients with IPF receiving antifibrotic drugs. This retrospective study enrolled Japanese patients who visited Toho University Sakura Medical Center who were diagnosed with IPF and received antifibrotic drugs. We included 102 patients [mean age ± standard deviation (SD): 71.8 ± 7.5years], of whom 76 were males. The decline in forced vital capacity (mean ± SD) during the antifibrotic therapy period was - 154 ± 259mL/year, which was significantly lower than before the antifibrotic therapy period (- 484 ± 589mL/year; n = 80, p = 0.003). Altogether, 52 deaths were confirmed, and the median survival time from antifibrotic therapy initiation was 38.0months (95% confidence interval: 25.9-50.1months). Acute exacerbation accounted for 9.6% of all deaths (95% confidence interval: 1.6-17.6). The decline in forced vital capacity during antifibrotic therapy was a risk factor for mortality. In actual clinical practice in Japan, antifibrotic drugs suppressed the gradual decline in forced vital capacity, which is a risk factor for mortality. However, the median survival period remained poor at 38months.

Efficacy and Safety of Nintedanib in Patients with Interstitial Lung Disease with or without Systemic Sclerosis: A Meta-Analysis.

Nintedanib is a potent intracellular inhibitor of tyrosine kinases and modulates the pathways involved in the development of fibrosis. We assessed nintedanib efficacy and safety in interstitial lung disease (ILD) patients. We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register to identify available articles (up to April 2022). We conducted a meta-analysis of randomized controlled trials (RCTs) examining nintedanib efficacy and safety in patients with ILD with or without systemic sclerosis (SSc). Meta-analysis of five RCTs including 2,470 patients with ILD (1,343 nintedanib group and 1,127 controls) revealed that the annual rate of change in forced vital capacity (FVC) was significantly lower in the ILD group than in the control group (standardized mean difference [SMD] = 0.336; 95% confidence interval (CI) = 0.256-0.416, P<0.001). Stratification by disease type showed a low annual rate of change in FVC in patients with and without SSc (SMD = 0.389, 95% CI=0.294-0.478, P<0.001; SMD=0.177, 95% CI=0.013-0.340, P<0.00). The incidence of serious adverse events did not differ between the nintedanib and placebo groups; however, adverse events (AEs) and withdrawals due to AEs were significantly higher in the nintedanib group than in the placebo group (SMD =2.365, 95% CI=1.673-3.343, P<0.001; SMD =1.740, 95% CI= 1.385-2.185, P<0.001). Nintedanib is effective for ILD with or without SSc. However, it increased the incidence of AEs and withdrawals due to AEs.

Decline in forced vital capacity in subjects with systemic sclerosis-associated interstitial lung disease in the SENSCIS trial compared with healthy reference subjects

BackgroundThe forced vital capacity (FVC) of healthy individuals depends on their age, sex, ethnicity and height. Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterised by loss of FVC. We compared FVC values in the subjects with SSc-ILD in the SENSCIS trial of nintedanib versus placebo with values from hypothetical matched healthy references.MethodsThe SENSCIS trial enrolled subjects with SSc with first non-Raynaud symptom in the prior ≤ 7 years, extent of fibrotic ILD on HRCT ≥ 10%, and FVC ≥ 40% predicted. FVC at baseline and decline in FVC over 52 weeks were compared with FVC values in hypothetical healthy reference subjects matched 1:1 to the subjects in the trial for age, sex, ethnicity and height, determined using equations published by the European Respiratory Society Global Lung Function Initiative.ResultsAt baseline, mean (SD) FVC was 2460 (737) mL in the nintedanib group (n = 287) compared with 3403 (787) mL in the hypothetical matched healthy references. Mean (SD) FVC was 2544 (817) mL in the placebo group (n = 286) compared with 3516 (887) mL in the hypothetical matched healthy references. Mean (SE) changes in FVC at week 52, i.e., age-related loss of lung function, in the hypothetical healthy references matched to the nintedanib and placebo groups, respectively, were − 26.3 (0.5) mL and − 25.8 (0.5) mL. The difference in the change in FVC at week 52 between the nintedanib group and the hypothetical healthy references was 26.6 mL (95% CI: 1.2, 52.0; p = 0.04). The difference in the change in FVC at week 52 between the placebo group and the hypothetical healthy references was 77.5 mL (95% CI: 51.4, 103.7; p < 0.0001).ConclusionsSubjects with SSc-ILD in the SENSCIS trial had impaired lung function at baseline and experienced further deterioration over 52 weeks. The decline in FVC in the placebo group was four-fold greater than in a hypothetical group of matched healthy references, whereas the decline in FVC in patients who received nintedanib was two-fold greater than in hypothetical healthy references. These data highlight the clinical relevance of the slowing of FVC decline provided by nintedanib.Trial registration Registered 5 November 2015, https://clinicaltrials.gov/ct2/show/NCT02597933.

Role of transient receptor potential vanilloid 4 in therapeutic antifibrotic effects of pirfenidone.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fatal lung disorder characterized by aberrant extracellular matrix deposition in the interstitium. Pirfenidone is an antifibrotic agent used to treat patients with IPF. Pirfenidone shows a pleiotropic mode of action, but its underlying antifibrotic mechanism is unclear. Transient receptor potential vanilloid 4 (TRPV4), which is a mechanosensitive calcium channel, was recently shown to be related to pulmonary fibrosis. To clarify the antifibrotic mechanisms of pirfenidone, we investigated whether TRPV4 blockade has a pharmacological effect in a murine model of pulmonary fibrosis and whether pirfenidone contributes to suppression of TRPV4. Our synthetic TRPV4 antagonist and pirfenidone treatment attenuated lung injury in the bleomycin mouse model. TRPV4-mediated increases in intracellular calcium were inhibited by pirfenidone. In addition, TRPV4-stimulated interleukin-8 release from cells was reduced and a delay in cell migration was abolished by pirfenidone. Furthermore, pirfenidone decreased TRPV4 endogenous ligands in bleomycin-administered mouse lungs and their production by microsomes of human lungs. We found TRPV4 expression in the bronchiolar and alveolar epithelium and activated fibroblasts of the lungs in patients with IPF. Finally, we showed that changes in forced vital capacity of patients with IPF treated with pirfenidone were significantly correlated with metabolite levels of TRPV4 endogenous ligands in bronchoalveolar lavage fluid. These results suggest that the antifibrotic action of pirfenidone is partly mediated by TRPV4 and that TRPV4 endogenous ligands in bronchoalveolar lavage fluid may be biomarkers for distinguishing responders to pirfenidone.

POS0070 CONTINUED TREATMENT WITH NINTEDANIB IN PATIENTS WITH LIMITED CUTANEOUS SYSTEMIC SCLEROSIS (lcSSc) AND INTERSTITIAL LUNG DISEASE (ILD)

POS0070 CONTINUED TREATMENT WITH NINTEDANIB IN PATIENTS WITH LIMITED CUTANEOUS SYSTEMIC SCLEROSIS (lcSSc) AND INTERSTITIAL LUNG DISEASE (ILD)

Influence of β2 adrenergic receptor genotype on longitudinal measures of forced vital capacity in patients with Duchenne muscular dystrophy

The progression of decline in forced vital capacity as percent predicated (FVC%p) is a strong indicator of worsening prognosis in patients with Duchenne muscular dystrophy (DMD). Evidence suggests that ß2 adrenergic (ADRB2) receptors may play a role in determining respiratory function, whereby more functional ADRB2 genotype variants (e.g., Gly16) are associated with improved pulmonary function. The purpose of this study was to determine the influence of ADRB2 genotype on longitudinal measures of FVC%p as a function of age in DMD patients. Data from the CINRG Duchenne Natural History Study including 169 DMD patients (5–25 yrs) were analyzed. A generalized additive mixed effects model was used to examine differences in the nonlinear trend of FVC%p across patient ages between genotype groups after controlling for patient demographics, corticosteroid-use, and ambulatory status. Both genotype groups displayed a progressive, maturational decline in FVC%p. Notwithstanding this decline, patients expressing the Gly16 polymorphism demonstrated systematically lower FVC%p values at any given age compared with patients expressing the Arg16 polymorphism (P < 0.01). Therefore, expressing the Gly16 polymorphism may prove detrimental to respiratory function in DMD patients. These data suggest maybe ADRB2 genotyping should be considered in the clinical management of DMD patients.

Progression of Idiopathic Pulmonary Fibrosis Is Associated with Silica/Silicate Inhalation

Recently, environmental dust exposure has emerged as a possible risk factor for interstitial pneumonia. Inhaled silica/silicates and titanium are associated with the progression of rapidly progressive pneumoconiosis. However, the relationship between inhaled elements and idiopathic pulmonary fibrosis (IPF) remains unclear. In this study, we focused on IPF presenting with histological usual interstitial pneumonia and investigated the relationship between inhaled elements and IPF progression. We examined the elements in the lungs using in-air micro-particle-induced X-ray emission analysis (PIXE). Lung tissue samples with IPF were analyzed and compared with control lung samples. There was a significant difference between IPF and the control lungs in terms of silicon, assumed to form silica/silicates. Inhaled silicon in the lungs significantly correlated with the annual decline in forced vital capacity in patients with IPF. Furthermore, IPF patients with higher accumulation of silicon showed a significantly poorer prognosis than those with lower accumulation of silicon in the lungs. These significant differences were also seen in multivariate analyses, including smoking history, IPF severity, and/or antifibrotic treatment. In-air micro-PIXE can be beneficial for detecting inhaled elements in the lung. These results indicate that inhaled silica/silicates in the lung may be partly involved in the progression of IPF.

Exposure\u2013safety analyses of nintedanib in patients with chronic fibrosing interstitial lung disease

BackgroundNintedanib reduces the rate of decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF), other chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype and systemic sclerosis-associated ILD (SSc-ILD). The recommended dose of nintedanib is 150 mg twice daily (BID).MethodsData from Phase II and III trials in IPF and Phase III trials in SSc-ILD and progressive fibrosing ILDs other than IPF were analyzed to investigate the relationship between nintedanib plasma concentrations (exposure) and safety (liver enzyme elevations [defined as transaminase elevations equal or greater than 3 times the upper limit of normal] and diarrhea).ResultsUsing data from 1403 subjects with IPF treated with 50–150 mg nintedanib BID, a parametric time-to-first-event model for liver enzyme elevations was established. Besides exposure, gender was a significant covariate, with a three–fourfold higher exposure-adjusted risk in females than males. Subsequent analysis of combined data from IPF, SSc-ILD (n = 576) and progressive fibrosing ILD (n = 663) studies suggested a consistent exposure–liver enzyme elevation relationship across studies. No exposure–diarrhea relationship was found using data from the various fibrosing ILDs, but diarrhea risk was dependent on dose administered.ConclusionsThe positive correlation between exposure and risk of liver enzyme elevations was consistent across nintedanib studies in IPF, SSc-ILD and progressing fibrosing ILDs other than IPF. The effect size does not warrant a priori dose adjustment in patients with altered plasma exposure (excluding hepatic impairment patients, where there are specific labelling recommendations). For diarrhea, dose administered was a better predictor than exposure.

OP0124 EFFECTS OF NINTEDANIB IN PATIENTS WITH PROGRESSIVE FIBROSING INTERSTITIAL LUNG DISEASE ASSOCIATED WITH RHEUMATOID ARTHRITIS (RA-ILD) IN THE INBUILD TRIAL

Background:In the INBUILD trial in subjects with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF), nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks by 57% compared with placebo.Objectives:To assess the rate of decline in FVC in subjects with RA-ILD in the INBUILD trial.Methods:Subjects in the INBUILD trial had a chronic fibrosing ILD other than IPF, reticular abnormality with traction bronchiectasis (with or without honeycombing) of &gt;10% extent on high-resolution computed tomography (HRCT), forced vital capacity (FVC) ≥45% predicted, diffusing capacity of the lungs for carbon monoxide ≥30%–&lt;80% predicted, and met criteria for progression of ILD within the 24 months before screening, despite management deemed appropriate in clinical practice. Patients taking stable doses of approved medications to treat RA or connective tissue disease could participate, except that the protocol excluded those taking azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, rituximab, cyclophosphamide, or oral glucocorticoids &gt;20 mg/day. We analysed the rate of decline in FVC (mL/year) over 52 weeks and adverse events in subjects with RA-ILD.Results:Of 663 subjects who received trial medication, 89 had RA-ILD (42 nintedanib, 47 placebo), of whom 60.7% were male, 64.0% were current or former smokers, 86.5% had a usual interstitial pneumonia (UIP)-like pattern on HRCT; 93.3% had received confirmation of their RA diagnosis from a rheumatologist. At baseline, 21.3% of subjects were taking biologic disease-modifying anti-rheumatic drugs (DMARDs), 53.9% were taking non-biologic DMARDs and 73.0% were taking glucocorticoids (≤20 mg/day prednisone or equivalent). At baseline, mean (SD) age was 66.9 (9.6) years, time since RA diagnosis was 9.9 (9.4) years, time since ILD diagnosis was 3.6 (3.2) years, FVC was 71.5 (16.2) % predicted and C-reactive protein was 13.7 (22.5) mg/L. The adjusted mean (SE) rate of decline in FVC over 52 weeks was -82.6 (41.3) mL/year in the nintedanib group versus -199.3 (36.2) mL/year in the placebo group (difference 116.7 mL/year [95% CI 7.4, 226.1]; nominal p=0.037), consistent with findings in the overall trial population (Figure). As in the overall trial population, the most common adverse event in subjects with RA-ILD was diarrhoea (reported in 54.8% of the nintedanib group and 25.5% of the placebo group). Adverse events led to permanent discontinuation of trial drug in 19.0% of subjects in the nintedanib group and 12.8% of subjects in the placebo group.Conclusion:In the INBUILD trial, nintedanib slowed the rate of decline in FVC in patients with progressive fibrosing RA-ILD, with adverse events that were manageable for most patients. The efficacy and safety of nintedanib in subjects with RA-ILD were consistent with those observed in the overall trial population.Acknowledgements:The INBUILD trial was funded by Boehringer Ingelheim. Medical writing support was provided by Fleishman Hillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Clive Kelly Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Eric Matteson Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim and Gilead Sciences, Grant/research support from: Sun Pharmaceuticals and Pfizer, Martin Aringer Speakers bureau: AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai, Gilead, GlaxoSmithKline, HEXAL, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi and UCB, Consultant of: AbbVie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Lilly, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Sanofi and UCB, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Lilly, Merck Sharp &amp; Dohme, Pfizer, Roche and Sanofi, Consultant of: AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead, Lilly, Merck Sharp &amp; Dohme, Pfizer, Roche and Sanofi, Heiko Mueller Employee of: Currently an employee of Boehringer Ingelheim, Lizette Moros Employee of: Currently an employee of Boehringer Ingelheim, Klaus Rohr Employee of: Currently an employee of Boehringer Ingelheim, Martin Kolb Consultant of: Algernon, Boehringer Ingelheim, Pieris Pharmaceuticals and Roche, Grant/research support from: Boehringer Ingelheim, Pieris Pharmaceuticals and Prometic

The safety of nintedanib for the treatment of interstitial lung disease: A systematic review and meta-analysis of randomized controlled trials.

IntroductionNintedanib can inhibit processes involved in the progression of fibrosis and can reduce the decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic-interstitial lung disease (fibrotic-ILDs). Although the adverse events associated with nintedanib in IPF patients are well known, its safety in other fibrotic-ILD patients remained unclear.MethodsWe searched PubMed, EMBASE, Cochrane CENTRAL and Cochrane CDSR for randomized controlled studies which compared nintedanib with a placebo in ILD patients. We estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs) for adverse events using the DerSimonian–Laird random-effects model.ResultsSix studies with a total of 2,583 patients were included in the meta-analysis. The pooled estimates showed that patients treated with nintedanib had a significantly higher likelihood of having any adverse events (OR = 2.39; 95% CI = 1.71–3.36) or adverse events leading to treatment discontinuation (OR = 1.73; 95% CI = 1.34–2.25). However, they had trend to lower likelihood of having fatal adverse events (OR = 0.69; 95% CI = 0.41–1.14) compared with the placebo group. Use of nintedanib was positively associated with diarrhea (OR = 5.96; 95% CI = 4.35–8.16), nausea (OR = 3.00; 95% CI = 1.93–4.66), vomiting (OR = 3.22; 95% CI = 2.17–4.76) and weight loss (OR = 3.38; 95% CI = 1.1.76–6.47). Whereas, patients treated with nintedanib were less likely to have a cough (OR = 0.73; 95% CI = 0.56–0.96) and dyspnea (OR = 0.70; 95% CI = 0.53–0.94).ConclusionsCompared to a placebo, nintedanib was associated with a higher risk of adverse events, especially for diarrhea, nausea, vomiting and weight loss, but it was also associated with a lower risk of cough and dyspnea in IPF and fibrotic-ILD patients.

Current and future treatment for idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrosing interstitial lung disease, which is associated with a short survival rate. The decline in forced vital capacity in patients with IPF appears to be almost the same rate regardless of baseline lung function status. This suggests that early treatment would be necessary to prevent further deterioration even lung function is maintained within normal limits. Both pirfenidone and nintedanib significantly slow the decline in lung function, reduce the risk of acute exacerbation, and improve survival rate. However, many individuals with IPF remain untreated. Most IPF patients can tolerate antifibrotic drug therapy, and the dose adjustment has been shown to effectively reduce side effects without modifying efficacy. Although the recent introduction of pirfenidone and nintedanib has led to the slowing of lung function decline, there is no evidence of fibrosis reversal. In the near future, several new drugs are expected to be prescribed to patients with IPF. We are anticipating that some drugs may reverse fibrosis. Fibrosis inhibiting drugs have different pharmacological actions and there are various mechanisms causing fibrosis in the lesion. Therefore, it is imperative to launch efforts to optimize antifibrotic effects through a combination therapy of several drugs. These efforts will hold out hope for patients with IPF.

Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trial

In the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial, nintedanib reduced the rate of decline in forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). Patients on stable treatment with mycophenolate for at least 6 months before randomisation could participate. The aim of this subgroup analysis was to examine the efficacy and safety of nintedanib by mycophenolate use at baseline. The SENSCIS trial was a randomised, double-blind, placebo-controlled trial, in which patients with SSc-ILD were randomly assigned (1:1) to receive 150 mg of oral nintedanib twice daily or placebo for at least 52 weeks. In a prespecified subgroup analysis, we analysed the primary endpoint of rate of decline in FVC over 52 weeks by mycophenolate use at baseline. In a post-hoc analysis, we analysed the proportion of patients with an absolute decrease in FVC of at least 3·3% predicted at week 52 (proposed minimal clinically important difference estimate for worsening of FVC in patients with SSc-ILD) in subgroups by mycophenolate use at baseline. Adverse events were reported in subgroups by mycophenolate use at baseline. Analyses were done in all participants who received at least one dose of study drug. We analysed the annual rate of decline in FVC using a random coefficient regression model (with random slopes and intercepts) including anti-topoisomerase I antibody status, age, height, sex, and baseline FVC as covariates and terms for baseline-by-time, treatment-by-subgroup, and treatment-by-subgroup-by-time interactions. SENSCIS is registered with ClinicalTrials.gov, NCT02597933, and is now complete. Between Nov 30, 2015, and Oct 31, 2017, 819 participants were screened and 576 were enrolled, randomly assigned to, and treated with nintedanib (n=288) or placebo (n=288). 139 (48%) of 288 in the nintedanib group and 140 (49%) of 288 in the placebo group were taking mycophenolate at baseline. In patients taking mycophenolate at baseline, the adjusted mean annual rate of decline in FVC was -40·2 mL per year (SE 19·8) with nintedanib and -66·5 mL per year (19·3) with placebo (difference: 26·3 mL per year [95% CI -27·9 to 80·6]). In patients not taking mycophenolate at baseline, the adjusted mean annual rate of decline in FVC was -63·9 mL per year (SE 19·3) with nintedanib and -119·3 mL per year (19·0) with placebo (difference: 55·4 mL per year [95% CI 2·3 to 108·5]). We found no heterogeneity in the effect of nintedanib versus placebo on the annual rate of decline in FVC between the subgroups by mycophenolate use (p value for interaction=0·45). In a post-hoc analysis, the proportion of patients with an absolute decrease in FVC of at least 3·3% predicted was lower with nintedanib than with placebo in both patients taking mycophenolate (40 [29%] of 138 vs 56 [40%] of 140; odds ratio 0·61 [0·37 to 1·01]) and those not taking mycophenolate (59 [40%] of 149 vs 70 [47%] of 148; 0·73 [0·46 to 1·16]) at baseline. The adverse event profile of nintedanib was similar between the subgroups. Diarrhoea, the most common adverse event, was reported in 106 (76%) of 139 patients in the nintedanib group and 48 (34%) of 140 in the placebo group among those taking mycophenolate at baseline, and in 112 (75%) of 149 in the nintedanib group and 43 (29%) of 148 in the placebo group among those not taking mycophenolate at baseline. Over the entire trial period, 19 patients died (ten in the nintedanib group and nine in the placebo group). One death in the nintedanib group was considered to be related to study drug. Nintedanib reduced the progression of interstitial lung disease both in patients with SSc-ILD who were and were not using mycophenolate at baseline, with no heterogeneity in its treatment effect detected between the subgroups. The adverse event profile of nintedanib was similar in the subgroups by mycophenolate use. Our findings suggest that the combination of mycophenolate and nintedanib offers a safe treatment option for patients with SSc-ILD. More data are needed on the benefits of initial combination therapy versus a sequential approach to treatment of SSc-ILD. Boehringer Ingelheim.

Role of Forced Expiratory Volume in Third second (FEV3) as An Alternative to Forced Vital Capacity (FVC) in Assessing Bronchodilator Response in Patients with Chronic Obstructive Airway Diseases

Background: Spirometry is a physiological procedure used as a diagnostic tool for disease diagnosis; e.g. obstructive pulmonary diseases such as asthma or chronic obstructive pulmonary disease (COPD). The bronchodilator test is a method of measuring lung capacity changes following inhalation of a short-acting bronchodilator drug that dilates the airway, this test helps to diagnose, evaluate and differentiate asthma from COPD. Objective: To evaluate the role of forced expiratory volume in third second (FEV3) as an alternative for forced vital capacity (FVC) in assessing bronchodilator response in patients with chronic obstructive airway diseases. Methods: The study a case-control, comparative study done from November 2018 to November 2019. The cases involved divided into 2 groups; patients group included (80) patients with chronic obstructed pulmonary diseases (asthma and COPD) and control group included (160) apparently healthy peoples aged and sex matched. Lung function was measured using a standard protocol and electronic table spirometry. Bronchodilator test was done for each patient with chronic obstructed defect on spirometer. Results: There was no significant difference between (FVC), FVC% and (FEV3), FEV3% respectively before bronchodilator and there was no significant difference after bronchodilator in patients. There was no significant difference between FEV1/FVC, FEV1/FVC % and FEV1/ FEV3, FEV1/FEV3% respectively before bronchodilator and there was no significant difference after bronchodilator in patients. Conclusion: FEV3 can be used as an alternative to FVC in patients with chronic obstructive airway diseases for assessing bronchodilator response. Keywords: Spirometry, Bronchodilator test, FVC%, FEV3%, FEV1/FVC%, FEV1/FEV3% Citation: Jizar AY, Hashim ZH, Jasim AH. Role of forced expiratory volume in third second (FEV3) as an alternative to forced vital capacity (FVC) in assessing bronchodilator response in patients with chronic obstructive airway diseases. Iraqi JMS. 2020; 18(2): 94-100. doi: 10.22578/IJMS.18.2.2

The association of impaired lung function and nonalcoholic fatty liver disease: a systematic review.

Nonalcoholic fatty liver disease (NAFLD) and impaired lung function share similar risk factors and phenotypes, such as obesity and type 2 diabetes. The study is an updated meta-analysis to evaluate the association between NAFLD and impaired lung function. A total of 696 articles were identified with mention of NAFLD and lung function (or pulmonary function testing) in MEDLINE, EMBASE, and Scopus. After de-duplication, 455 articles were screened, 18 underwent full-text review. Five studies met our review and inclusion criteria with an interrater reliability kappa score of 1. Five studies with a total of 118 118 subjects (28.4% with NAFLD) were included. The cross-sectional studies supported a statistically significant relationship between decreased pulmonary function tests and NAFLD. There was no association observed with obstructive lung pattern. One of the longitudinal studies revealed an association with increased rate of decline in forced vital capacity in patients with NAFLD and FIB4 score ≥1.30 (-21.7 vs. -27.4 mL/year, P = 0.001 in males, -22.4 vs. -27.9 mL/year, P = 0.016 in females). The second longitudinal study revealed that patients with impaired pulmonary function had an increased hazard ratio of developing NAFLD dependent on the severity of pulmonary impairment. This is the first systematic review that supports an association of NAFLD with decreased (restrictive) lung function. The estimated severity of liver fibrosis correlates with the rate of progression of restrictive lung function. There are also data showing that patients with impaired lung function have a higher risk of developing NAFLD.

Effectiveness of pirfenidone for idiopathic pulmonary fibrosis associated with pleuroparenchymal fibroelastosis-like lesions and nonspecific interstitial pneumonia.

Pirfenidone treatment can slow decline in forced vital capacity (FVC) in idiopathic pulmonary fibrosis (IPF). However, its effects for usual interstitial pneumonia (UIP) with pleuroparenchymal fibroelastosis-like lesions (UIP+PPFELL) and UIP with nonspecific interstitial pneumonia (UIP+NSIP) are unclear. The aim of study is to assess pirfenidone effectiveness for UIP+PPFELL and UIP+NSIP. We retrospectively analysed data from 58 IPF patients treated with pirfenidone more than 6 months. The outcomes of interest were 6-month follow-up pulmonary function test results, progression-free survival (PFS) and overall survival (OS). Treatment was considered effective if FVC decline was <5% during the 6-month period. We compared clinical characteristics, effectiveness, PFS and OS between patients with typical IPF (n=32), UIP+PPFELL (n=12) and UIP+NSIP (n=14). Data from 58 IPF patients were analysed. At the 6-month follow-up examination, treatment was deemed effective for 9 of 14 (64%) UIP+NSIP patients, 6 of 12 (50%) UIP+PPFELL patients and 14 of 32 (44%) patients with typical IPF. The 6-month decline in FVC before treatment was greater than that after starting treatment in the UIP+NSIP (-210 vs. -57mL; P=0.09), UIP+PPFELL (-370 vs. -89mL; P=0.001) and typical IPF (-172 vs. -85mL; P=0.37). PFS did not significantly differ between the three groups. OS was significantly shorter for UIP+PPFELL (312days) than for UIP+NSIP (545days) and typical IPF (661days). Pirfenidone decreased the decline in FVC in patients with UIP+PPFELL and UIP+NSIP, as well as in those with typical IPF. However, outcomes were worse for patients with UIP+PPFELL.

Safety and tolerability of nintedanib in patients with systemic sclerosis-associated interstitial lung disease: data from the SENSCIS trial

ObjectivesTo characterise the safety and tolerability of nintedanib and the dose adjustments used to manage adverse events in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).MethodsIn the SENSCIS trial, patients...

FEV1 is a stronger mortality predictor than FVC in patients with moderate COPD and with an increased risk for cardiovascular disease.

PurposeChronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD exacerbations. However, it is unclear if forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) differ in predictive value.Patients and MethodsData from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed. Patients were grouped into quintiles for each lung function parameter (FEV1 %predicted, FVC %predicted, FEV1/FVC). The four highest quintiles (Q2–Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations. Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score.ResultsCompared to Q1 (<53.5% FEV1 predicted), increasing FEV1 quintiles (Q2 53.5–457.5% predicted, Q3 57.5–461.6% predicted, Q4 61.6–465.8% predicted, and Q5 ≥65.8%) were all associated with significantly decreased all-cause mortality (20% (4–34%), 28% (13–40%), 23% (7–36%), and 30% (15–42%) risk reduction, respectively). In contrast, a significant risk reduction (21% (4–35%)) was seen only between Q1 and Q5 quintiles of FVC. Neither FEV1 nor FVC was associated with cardiovascular risk. Increased FEV1 and FEV1/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8–52%) risk increase).ConclusionOur results suggest that FEV1 is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks.