Home spirometry in patients with idiopathic pulmonary fibrosis: data from the INMARK trial.
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ABSTRACT: Background
Data from the INMARK trial were used to investigate the feasibility and validity of home spirometry as a measure of lung function decline in patients with idiopathic pulmonary fibrosis (IPF).Methods
Subjects with IPF and preserved forced vital capacity (FVC) were randomised to receive nintedanib or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Clinic spirometry was conducted at baseline and weeks 4, 8, 12, 16, 20, 24, 36 and 52. Subjects were asked to perform home spirometry at least once a week and ideally daily. Correlations between home- and clinic-measured FVC and rates of change in FVC were assessed using Pearson correlation coefficients.Results
In total, 346 subjects were treated. Mean adherence to weekly home spirometry decreased over time but remained above 75% in every 4-week period. Over 52 weeks, mean adherence was 86%. Variability in change from baseline in FVC was greater when measured by home rather than clinic spirometry. Strong correlations were observed between home- and clinic-measured FVC at all time-points (r=0.72-0.84), but correlations between home- and clinic-measured rates of change in FVC were weak (r=0.26 for rate of decline in FVC over 52 weeks).Conclusion
Home spirometry was a feasible and valid measure of lung function in patients with IPF and preserved FVC, but estimates of the rate of FVC decline obtained using home spirometry were poorly correlated with those based on clinic spirometry.
SUBMITTER: Noth I
PROVIDER: S-EPMC8264778 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:RationaleRecent clinical trial successes have created an urgent need for earlier and more sensitive endpoints of disease progression in idiopathic pulmonary fibrosis (IPF). Domiciliary spirometry permits more frequent measurement of FVC than does hospital-based assessment, which therefore affords the opportunity for a more granular insight into changes in IPF progression.ObjectivesTo determine the feasibility and reliability of measuring daily FVC in individuals with IPF.MethodsSubjects with IPF were given handheld spirometers and instruction on how to self-administer spirometry. Subjects recorded daily FEV1 and FVC for up to 490 days. Clinical assessment and hospital-based spirometry was undertaken at 6 and 12 months, and outcome data were collected for 3 years.Measurements and main resultsDaily spirometry was recorded by 50 subjects for a median period of 279 days (range, 13-490 d). There were 18 deaths during the active study period. Home spirometry showed excellent correlation with hospital-obtained readings. The rate of decline in FVC was highly predictive of outcome and subsequent mortality when measured at 3 months (hazard ratio [HR], 1.040; 95% confidence interval [CI], 1.021-1.062; P ≤ 0.001), 6 months (HR, 1.024; 95% CI, 1.014-1.033; P < 0.001), and 12 months (HR, 1.012; 95% CI, 1.007-1.016; P = 0.001).ConclusionsMeasurement of daily home spirometry in patients with IPF is highly clinically informative and is feasible to perform for most of these patients. The relationship between mortality and rate of change of FVC at 3 months suggests that daily FVC may be of value as a primary endpoint in short proof-of-concept IPF studies.
| S-EPMC5067818 | biostudies-literature
Project description:The objective of this study was to investigate the reliability, feasibility and analytical impact of home-based measurement of forced vital capacity (FVC) and dyspnoea as clinical endpoints in idiopathic pulmonary fibrosis (IPF).Patients with IPF performed weekly home-based assessment of FVC and dyspnoea using a mobile hand-held spirometer and self-administered dyspnoea questionnaires. Weekly variability in FVC and dyspnoea was estimated, and sample sizes were simulated for a hypothetical 24-week clinical trial using either traditional office-based interval measurement or mobile weekly assessment.In total, 25 patients were enrolled. Mean adherence to weekly assessments over 24?weeks was greater than 90%. Compared with change assessment using baseline and 24-week measurements only, weekly assessment of FVC resulted in enhanced precision and power. For example, a hypothetical 24-week clinical trial with FVC as the primary endpoint would require 951 patients using weekly home spirometry compared with 3840 patients using office spirometry measures at weeks 1 and 24 only. The ability of repeated measures to reduce clinical trial sample size was influenced by the correlation structure of the data.Home monitoring can improve the precision of endpoint assessments, allowing for greater efficiency in clinical trials of therapeutics for IPF.
| S-EPMC6029860 | biostudies-literature
Project description:We report the implementation of a pediatric home spirometry program at our institution. A respiratory therapist provided either a virtual or an in-person initiation visit that included a coached spirometry session. Families were instructed to perform daily uncoached spirometry sessions for 5 days. The program's quality assurance component was deemed not to be human research by the local IRB. In total, 52 subjects completed an initiation visit (34 with at least 3 additional uncoached spirometry sessions). The clinic spirometry and coached (same-day) sessions and uncoached (same-week) sessions were completed by 12 and 17 subjects, respectively. The median (99% CI) coefficients of variation for FEV1% of the uncoached maneuvers were 3.5% (2.9-5.9%). The median (IQR) FEV1% and FEV1 (mL) absolute differences between coached and uncoached home spirometry were -2% (-4 and +3%) and -25 mL (-93 and +93 mL), respectively. The median (IQR) absolute differences in FEV1% and FEV1 (mL) between coached or uncoached home spirometry and clinic spirometry were -6% (-10 and -2%) and -155 mL (-275 and -88 mL), and -4% (-10 and +5%), and -110 mL (-280 and +9 mL), respectively. Differences in absolute FEV1 (L) and FEV1% were found among different modalities of spirometry performed by people with cystic fibrosis. Understanding the variability of uncoached home spirometry and the differences among coached and uncoached home spirometry, hospital and coached home spirometry, and hospital and uncoached home spirometry for any given individual is crucial to effectively utilize this tool in clinical care.
| S-EPMC9952128 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is an untreatable fibrotic lung disease characterized by fibroblast proliferation and epithelial mesenchymal transition. The expression and role of microRNAs (miRNA) has not been studied in IPF. Using miRNA expression microarrays we identified 46 differentially expressed miRNA in IPF lungs which included let-7d and the miR-30 family. Keywords: miRNA expression Lung tissue samples for microarray analysis were obtained through the University of Pittsburgh Health Sciences Tissue Bank. Ten samples were obtained from surgical remnants of biopsies or lungs explanted from patients with IPF who underwent pulmonary transplant, and ten control normal lung tissues obtained from the disease free margins with normal histology of lung cancer resection specimens. The morphologic diagnosis of IPF was based on typical microscopic findings consistent with usual interstitial pneumonia. Total RNA was labeled with Cy3 and hybridized on Agilent 8X15K microRNA array (Agilent Technologies, Santa Clara, CA). After 20 hours hybridization, arrays were washed and scanned according to the manufacturerâs protocol.
2010-04-23 | E-GEOD-13316 | biostudies-arrayexpress
Project description:Idiopathic pulmonary fibrosis (IPF) is an untreatable fibrotic lung disease characterized by fibroblast proliferation and epithelial mesenchymal transition. Using miRNA expression microarrays we identified 96 differentially expressed miRNA in IPF lungs which included let-7d, miR-30 family, miR-29 family and miR-154 family. Lung tissue samples for microarray analysis were obtained through the University of Pittsburgh Health Sciences Tissue Bank. 13 samples were obtained from surgical remnants of biopsies or lungs explanted from patients with IPF who underwent pulmonary transplant, and 12 control normal lung tissues obtained from the disease free margins with normal histology of lung cancer resection specimens. The morphologic diagnosis of IPF was based on typical microscopic findings consistent with usual interstitial pneumonia. Total RNA was labeled with Cy3 and hybridized on Agilent 8X15K microRNA array (Agilent Technologies, Santa Clara, CA). After 20 hours hybridization, arrays were washed and scanned according to the manufacturer’s protocol.
2013-01-04 | E-GEOD-27430 | biostudies-arrayexpress
Project description:Idiopathic pulmonary fibrosis (IPF), a chronic progressive lung disease of unknown etiology, is characterized by the expansion of myofibroblasts and abnormal deposition of extracellular matrix in the lung parenchyma. To elucidate the molecular mechanisms that lead to IPF, we analyzed myofibroblasts established from patients with IPF by oligonucleotide microarrays. Gene expression profiles revealed a novel pathophysiologic function of myofibroblasts as a generator of reactive oxygen species, and a self-defense mechanism against oxidative stress of their own generating. Keywords: cell type comparison, disease state analysis
2008-01-17 | GSE6804 | GEO
Project description:Idiopathic pulmonary fibrosis (IPF) lacks effective treatment. Pirfenidone has been used to treat IPF patients. N-acetylcysteine (NAC) exerts antioxidant and antifibrotic effects on IPF cases.This study is a double-blind, modified placebo-controlled, randomized phase II trial of pirfenidone in Chinese IPF patients. We randomly assigned the enrolled Chinese IPF patients with mild to moderate impairment of pulmonary function to receive either oral pirfenidone (1800 mg per day) and NAC (1800 mg per day) or placebo and NAC (1800 mg per day) for 48 weeks. The primary endpoints were the changes in forced vital capacity (FVC) and walking distance and the lowest SPO2 during the 6-minute walk test (6MWT) at week 48. The key secondary endpoint was the progression-free survival time. This study is registered in ClinicalTrials.gov as number NCT01504334.Eighty-six patients were screened, and 76 cases were enrolled (pirfenidone + NAC: 38; placebo + NAC: 38). The effect of pirfenidone treatment was significant at the 24th week, but this effect did not persist to the 48th week. At the 24th week, the mean decline in both FVC and ?SPO2 (%) during the 6MWT in the pirfenidone group was lower than that in the control group (-0.08 ± 0.20 L vs -0.22 ± 0.29 L, P = 0.02 and -3.44% ± 4.51% vs -6.29% ± 6.06%, P = 0.03, respectively). However, there was no significant difference between these 2 groups at the 48th week (-0.15 ± 0.25 L vs -0.25 ± 0.28 L, P = 0.11 and -4.25% ± 7.27% vs -5.31% ± 5.49%, P = 0.51, respectively). The pirfenidone treatment group did not achieve the maximal distance difference on the 6MWT at either the 24th or the 48th week. But pirfenidone treatment prolonged the progression-free survival time in the IPF patients (hazard ratio = 1.88, 95% confidence interval: 1.092-3.242, P = 0.02). In the pirfenidone group, the adverse event (AE) rate (52.63%) was higher than that in the control group (26.3%, P = 0.03). Rash was more common in the pirfenidone group (39.5% vs 13.2%, P = 0.02).Compared with placebo combined with high-dose NAC, pirfenidone combined with high-dose NAC prolonged the progression-free survival of Chinese IPF patients with mild to moderate impairment of pulmonary function. (ClinicalTrials.gov number, NCT01504334).
| S-EPMC4620844 | biostudies-literature
Project description:This phase 2, randomised, double-blind, placebo-controlled trial evaluated the efficacy and safety of lebrikizumab, an interleukin (IL)-13 monoclonal antibody, alone or with background pirfenidone therapy, in patients with idiopathic pulmonary fibrosis (IPF).Patients with IPF aged ?40?years with forced vital capacity (FVC) of 40%-100% predicted and diffusing capacity for carbon monoxide of 25%-90% predicted and who were treatment-naïve (cohort A) or receiving pirfenidone (2403?mg·day-1; cohort B) were randomised 1:1 to receive lebrikizumab 250?mg or placebo subcutaneously every 4?weeks. The primary endpoint was annualised rate of FVC % predicted decline over 52?weeks.In cohort A, 154 patients were randomised to receive lebrikizumab (n=78) or placebo (n=76). In cohort B, 351 patients receiving pirfenidone were randomised to receive lebrikizumab (n=174) or placebo (n=177). Baseline demographics were balanced across treatment arms in both cohorts. The primary endpoint (annualised rate of FVC % predicted decline) was not met in cohort A (lebrikizumab versus placebo, -5.2% versus -6.2%; p=0.456) or cohort B (lebrikizumab versus placebo, -5.5% versus -6.0%; p=0.557). In cohort B, a non-statistically significant imbalance in mortality favouring combination therapy was observed (hazard ratio 0.42 (95% CI 0.17-1.04)). Pharmacodynamic biomarkers indicated lebrikizumab activity. The safety profile was consistent with that in previous studies of lebrikizumab and pirfenidone as monotherapies.Lebrikizumab alone or with pirfenidone was not associated with reduced FVC % predicted decline over 52?weeks despite evidence of pharmacodynamic activity. Lebrikizumab was well tolerated with a favourable safety profile. These findings suggest that blocking IL-13 may not be sufficient to achieve a lung function benefit in patients with IPF.
| S-EPMC7859504 | biostudies-literature
Project description:Acetylcysteine has been suggested as a beneficial treatment for idiopathic pulmonary fibrosis, although data from placebo-controlled studies are lacking.In our initial double-blind, placebo-controlled trial, we randomly assigned patients who had idiopathic pulmonary fibrosis with mild-to-moderate impairment in pulmonary function to receive a three-drug regimen of prednisone, azathioprine, and acetylcysteine; acetylcysteine alone; or placebo. The study was interrupted owing to safety concerns associated with the three-drug regimen. The trial continued as a two-group study (acetylcysteine vs. placebo) without other changes; 133 and 131 patients were enrolled in the acetylcysteine and placebo groups, respectively. The primary outcome was the change in forced vital capacity (FVC) over a 60-week period.At 60 weeks, there was no significant difference in the change in FVC between the acetylcysteine group and the placebo group (-0.18 liters and -0.19 liters, respectively; P=0.77). In addition, there were no significant differences between the acetylcysteine group and the placebo group in the rates of death (4.9% vs. 2.5%, P=0.30 by the log-rank test) or acute exacerbation (2.3% in each group, P>0.99).As compared with placebo, acetylcysteine offered no significant benefit with respect to the preservation of FVC in patients with idiopathic pulmonary fibrosis with mild-to-moderate impairment in lung function. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00650091.).
| S-EPMC4116664 | biostudies-literature
Project description:BackgroundHospitalizations are common among patients with idiopathic pulmonary fibrosis (IPF). We investigated the impact of hospitalizations on outcomes in patients with IPF.MethodsThe IPF-PRO Registry is an observational US registry that enrolled patients with IPF that was diagnosed or confirmed at the enrolling center in the previous 6 months. Associations between patient characteristics and hospitalization, and between hospitalization and mortality, were analyzed using Cox regression models.ResultsA total of 1002 patients with IPF were enrolled into the IPF-PRO Registry. Over a median follow-up time of 23.7 months (maximum: 67.0 months), 568 patients (56.7%) had at least one hospitalization. Of these patients, 319 (56.2%) had at least one respiratory-related hospitalization and 120 (21.1%) had at least one hospitalization with ventilatory support. Younger age (HR 0.68 [95% CI 0.55, 0.84] per 5-year increase for patients < 62 years), lower BMI (0.96 [0.93, 0.98] per 1-point increase), lower FVC % predicted (0.90 [0.83, 0.97] per 10% increase), oxygen use at rest (2.85 [2.18, 3.72]) and history of pulmonary hypertension (2.02 [1.37, 2.96]) at enrollment were associated with an increased risk of respiratory-related hospitalization during follow-up. In a multivariable model, there was an eightfold increase in the risk of mortality during hospitalization or within 90 days of discharge compared with outside of this period. The risk of mortality associated with a respiratory hospitalization or a hospitalization with ventilatory support was even greater.ConclusionsData from the IPF-PRO Registry demonstrate that hospitalizations are common among patients with IPF. The risk of mortality during hospitalization or within 90 days of discharge was high, particularly among patients who were hospitalized for a respiratory cause or received ventilatory support. Trial registration ClinicalTrials.gov, NCT01915511. Registered 5 August 2013, https://clinicaltrials.gov/ct2/show/NCT01915511.
| S-EPMC8481759 | biostudies-literature