Pirfenidone in fibrotic hypersensitivity pneumonitis: a double-blind, randomised clinical trial of efficacy and safety.

BACKGROUND: Fibrotic hypersensitivity pneumonitis (FHP) is an irreversible lung disease with high morbidity and mortality. We sought to evaluate the safety and effect of pirfenidone on disease progression in such patients. METHODS: We conducted a single-centre, randomised, double-blinded, placebo-controlled trial in adults with FHP and disease progression. Patients were assigned in a 2:1 ratio to receive either oral pirfenidone (2403 mg/day) or placebo for 52 weeks. The primary end point was the mean absolute change in the per cent predicted forced vital capacity (FVC%). Secondary end points included progression-free survival (PFS, time to a relative decline ≥10% in FVC and/or diffusing capacity of the lung for carbon monoxide (DLCO), acute respiratory exacerbation, a decrease of ≥50 m in the 6 min walk distance, increase or introduction of immunosuppressive drugs or death), change in FVC slope and mean DLCO%, hospitalisations, radiological progression of lung fibrosis and safety. RESULTS: After randomising 40 patients, enrolment was interrupted by the COVID-19 pandemic. There was no significant between-group difference in FVC% at week 52 (mean difference -0.76%, 95% CI -6.34 to 4.82). Pirfenidone resulted in a lower rate of decline in the adjusted FVC% at week 26 and improved PFS (HR 0.26, 95% CI 0.12 to 0.60). Results for other secondary end points showed no significant difference between groups. No deaths occurred in the pirfenidone group and one death (respiratory) occurred in the placebo group. There were no treatment-emergent serious adverse events. CONCLUSIONS: The trial was underpowered to detect a difference in the primary end point. Pirfenidone was found to be safe and improved PFS in patients with FHP. TRIAL REGISTRATION MUMBER: NCT02958917.

Design and rationale of a randomised, double-blind trial of the efficacy and safety of pirfenidone in patients with fibrotic hypersensitivity pneumonitis.

Hypersensitivity pneumonitis (HP) is an immunologically mediated form of lung disease resulting from inhalational exposure to any of a large variety of antigens. A subgroup of patients with HP develops pulmonary fibrosis (fibrotic HP; FHP), a significant cause of morbidity and mortality. This study will evaluate the safety and efficacy of the antifibrotic pirfenidone in treating FHP. This single-centre, randomised, double-blind, placebo-controlled trial is enrolling adults with FHP (ClinicalTrials.gov: NCT02958917). Study participants must have fibrotic abnormalities involving ≥5% of the lung parenchyma on high-resolution computed tomography scan, forced vital capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide ≥30% of predicted values. Study participants will be randomised in a 2:1 ratio to receive pirfenidone 2403 mg·day-1 or placebo. The primary efficacy end-point is the mean change in FVC % predicted from baseline to week 52. A number of secondary end-points have been chosen to evaluate the safety and efficacy in different domains.

Tracking dyspnea up to supplemental oxygen prescription among patients with pulmonary fibrosis.

BACKGROUND: Dyspnea is the hallmark symptom of pulmonary fibrosis. Supplemental oxygen (O2) is prescribed to many patients with pulmonary fibrosis in hopes of alleviating dyspnea and improving physical functioning. We used response data from the University of California San Diego Shortness of Breath Questionnaire (UCSD) which was administered monthly in the context of a longitudinal, observational study to plot a rich trajectory for dyspnea over time in patients with pulmonary fibrosis. We used other data from that study to identify clinical predictors of being prescribed O2 and to provide additional information for how UCSD scores could be used for clinical purposes. METHODS: We used linear mixed-effects models and multivariate Cox proportional hazards to model change in dyspnea scores over time and to identify significant predictors of time-to-O2-prescription among a pool of clinically-meaningful candidate variables. In the longitudinal study, all decisions, including whether or not to prescribe O2, were made by subjects' treating physicians, not members of the research team. RESULTS: One-hundred ninety-four subjects with pulmonary fibrosis completed more than one UCSD or were prescribed O2 at some point during the follow-up period (N = 43). Twenty-eight of the 43 had analyzable, longitudinal data and contribute data to the longitudinal UCSD analyses. All 43 were included in the time-to-O2-prescription analyses. Subjects prescribed O2 had more severe dyspnea at enrollment (38.4 ± 19.6 vs. 22.6 ± 18.7, p < 0.0001) and a steeper increase in UCSD scores over time (slope = 1.18 ± 0.53 vs. 0.24 ± 0.09 points per month, p = 0.02) than subjects not prescribed O2. Controlling for baseline UCSD score and FVC%, subjects with a clinical summary diagnosis of idiopathic pulmonary fibrosis (IPF) were far more likely to be prescribed O2 than subjects with other forms of pulmonary fibrosis (hazard ratio = 4.85, (2.19, 10.74), p < 0.0001). CONCLUSIONS: Baseline dyspnea and rise in dyspnea over time predict timing of O2 prescription. Accounting for disease severity, patients with IPF are more likely than patients with other forms of pulmonary fibrosis to be prescribed O2. UCSD scores provide clinically useful information; frequent administration could yield timely data on changes in disease status in patients with pulmonary fibrosis. TRIAL REGISTRATION: The longitudinal study is registered on ClinicalTrials.gov ( NCT01961362 ). Registered October 9, 2013.

Looking ahead and behind at supplemental oxygen: A qualitative study of patients with pulmonary fibrosis.

RATIONALE: Supplemental oxygen is prescribed to patients with pulmonary fibrosis to normalize oxygen saturations, decrease symptoms and improve quality of life. Along with potential benefits, patients face challenges as they incorporate oxygen into their lives. OBJECTIVE: Our aim was to better understand the perceptions and experiences of patients with pulmonary fibrosis as they confronted the possibility and realities of using supplemental oxygen. METHODS: We performed a mixed-methods study in which we conducted a series of four structured telephone interviews with five patients with pulmonary fibrosis enrolled in a longitudinal observational study. Questionnaires were administered at the time of the interviews, which were conducted at enrollment in the longitudinal study, immediately prior to starting supplemental oxygen, one month and then 9-12 months after starting oxygen. We used conventional content analysis to analyze interview data for themes within and across the four time points. RESULTS: Prior to starting supplemental oxygen, participants uniformly expected it would improve their physical function and quality of life. They also expected practical and psychological limitations, which after starting oxygen, they found to be more pronounced than anticipated. Despite the challenges, participants attributed benefits in symptoms, confidence and mobility to oxygen and came to a reluctant acceptance of it. Their expectations for guidance and support were inadequately met. CONCLUSIONS: For patients with pulmonary fibrosis, starting and using supplemental oxygen on an everyday basis confers benefits while also presenting a significant number of challenges. The process could be improved by providing them with clearer expectations and trustworthy educational resources. Oxygen case managers could help patients incorporate supplemental oxygen more seamlessly into their lives.

Informal caregivers experience of supplemental oxygen in pulmonary fibrosis.

BACKGROUND: Patients prescribed supplemental oxygen (O2) therapy face challenges as they adjust to being constantly "tethered" to an oxygen delivery device. Informal caregivers (ICs) of patients with pulmonary fibrosis (PF) face their own, often overlooked hardships when O2 is brought into their home and added to their lives. Our aim was to understand the multiple effects of supplemental oxygen therapy on ICs of patients with PF. METHODS: We conducted single, semi-structured telephone interviews with twenty ICs of patients with PF who were using O2 for at least 8 months. We performed a qualitative, content analysis based in grounded theory to examine data across subjects. RESULTS: ICs initially reacted to O2 with trepidation and sadness as they came to recognize the changes it would cause in the lives of their patient-loved one (PLO). ICs recognized both beneficial and negative effects of O2 on their PLOs. ICs also realized that O2 created significant changes in their own lives, including introducing new roles and responsibilities for them, altering their home environments and significantly impacting their relationships with their PLOs. Although O2 was a tangible and constant reminder of disease progression, over time ICs were able to adapt and accept their new lives with O2. CONCLUSION: ICs of patients with PF experience many life changes when their PLO is prescribed O2. Having O2 prescribers anticipate and recognize these challenges provides an opportunity to give support and guidance to ICs of PF patients who require O2 in the hopes of limiting the negative impact of O2 on their lives. TRIAL REGISTRATION: Clinicaltrials.gov , registration number NCT01961362 . Registered 9 October 2013.

Seeking and sharing: why the pulmonary fibrosis community engages the web 2.0 environment.

BACKGROUND: Pulmonary fibrosis (PF) is a rare, progressive disease that affects patients and their loved ones on many levels. We sought to better understand the needs and interests of PF patients and their loved ones (collectively "reader-participants") by systematically analyzing their engagement with the World Wide Web (the current version referred to as Web 2.0). METHODS: Data were collected from three PF-focused, interactive websites hosted by physician-investigators with expertise in PF. All data generated by reader-participants for approximately 10 months were downloaded and then analyzed using qualitative content analysis methods. RESULTS: PF experts posted 38 blog entries and reader-participants posted 40 forum entries. Blogs received 363 responses, and forum entries received 108 responses from reader-participants. Reader-participants primarily used the three websites to seek information from or offer a contribution to the PF community. Information was sought about PF symptoms, diagnosis, prognosis, treatments, research, pathophysiology, and disease origin; reader-participants also made requests for new posts and pleas for research and sought clarification on existing content. Contributions included personal narratives about experiences with PF, descriptions of activities or behaviors found to be helpful with PF symptoms, resources or information about PF, and supportive comments to other PF sufferers. CONCLUSIONS: PF patients and their loved ones engage the Web 2.0 environment at these PF-focused sites to satisfy their needs to better understand PF and its impacts and to support others facing similar challenges. Clinicians may find it beneficial to encourage PF patients' involvement in internet forums that foster dynamic, bi-directional information sharing.

Development of ATAQ-LAM: a tool to assess quality of life in Lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a progressive lung disease that impairs health-related quality of life (HRQL). OBJECTIVE: To develop and conduct initial testing of ATAQ-LAM (A Tool to Assess Quality of Life in LAM). METHODS: A pilot version of the questionnaire was administered to respondents with LAM. We used a deletion algorithm to retain items and then applied multi-trait scaling to place retained items into appropriate domains, thus generating the ATAQ-LAM. Rasch analysis was used to assess item fit to a unidimensional model of HRQL. We determined internal consistency (IC) and floor and ceiling effects of ATAQ-LAM scores and conducted analyses aimed at supporting the validity of ATAQ-LAM. RESULTS: Sixty-nine LAM patients provided response data. Thirty-two items survived the deletion algorithm. Scaling suggested ATAQ-LAM should have a four-domain structure (Exertional dyspnea, IC = 0.94; Cough, IC = 0.91; Fatigue, IC = 0.91; Emotional Well-Being, IC = 0.89). All items fit the Rasch model. Among 17 respondents with spirometry within three months of questionnaire completion, three of five ATAQ-LAM scores correlated with FEV1% (Exertional Dyspnea: r = -0.72, p = 0.001; Fatigue: r = -0.62, p = 0.007 and total: r = -0.53, p = 0.02). Compared with those in the highest tertile of FEV1%, subjects in the lowest tertile had greater ATAQ-LAM total (121.8 ± 14.3 vs. 79.8 ± 13.1, p = 0.04), Exertional Dyspnea (54.4 ± 6.3 vs. 25.5 ± 5.8, p = 0.005) and Fatigue (2.8 ± 2.4 vs. 14.8 ± 2.3, p = 0.03) scores, indicating greater impairment in HRQL. CONCLUSIONS: ATAQ-LAM is a disease-specific instrument designed to assess HRQL in LAM patients. Additional studies are needed to generate data in support of its validity as an instrument capable of assessing HRQL over time in LAM patients.

Protocol for a mixed-methods study of supplemental oxygen in pulmonary fibrosis.

BACKGROUND: Little is known about whether or how supplemental oxygen affects patients with pulmonary fibrosis. METHODS/DESIGN: A mixed-methods study is described. Patients with pulmonary fibrosis, informal caregivers of pulmonary fibrosis patients and practitioners who prescribe supplemental oxygen will be interviewed to gather data on perceptions of how supplemental oxygen impacts patients. In addition, three hundred pulmonary fibrosis patients who do not use daytime supplemental oxygen will be recruited to participate in a longitudinal, pre-/post- study in which patient-reported outcome (PRO) and activity data will be collected at baseline, immediately before daytime supplemental oxygen is initiated, and then once and again 9-12 months later. Activity data will be collected using accelerometers and portable GPS data recorders. The primary outcome is change in dyspnea from before to one month after supplemental oxygen is initiated. Secondary outcomes include scores from PROs to assess cough, fatigue and quality of life as well as the activity data. In exploratory analyses, we will use longitudinal data analytic techniques to assess the trajectories of outcomes over time while controlling for potentially influential variables. DISCUSSION: Throughout the study and at its completion, results will be posted on the website for our research program (the Participation Program for Pulmonary Fibrosis or P3F) at http://www.pulmonaryfibrosisresearch.org.

"Getting stuck with LAM": patients perspectives on living with lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease that affects almost exclusively women and is most often diagnosed before menopause. The main symptom of LAM is shortness of breath. LAM patients' perceptions of how the disease impacts their lives is largely unknown, but such information could be useful to generate patient reported outcome measures for use in drug trials (or other research studies) and to formulate interventions aimed at easing the burdens LAM imposes on patients. OBJECTIVE: To capture patients' perceptions of how LAM affects their lives. METHODS: We used reflexive team analysis to analyze transcripts from semi-structured focus groups conducted with LAM patients at LAMposium 2013. We sought to determine what patients perceive as the primary symptoms of LAM and how the disease affects them in their daily lives. RESULTS: The 37 participants described seven primary symptoms of LAM and five common psychological experiences from living with the disease. Shortness of breath and low energy (or fatigue) dominated the symptomatic picture; cough, sensations in the chest, difficulty sleeping, gastrointestinal issues, and mild cognitive difficulties were less common. The common psychological experiences participants reported included frustration, worry, loss of identity, embarrassment, and in some participants, a healthy defiance against the disease. CONCLUSIONS: Patients perceive the physical symptoms from LAM to be intrusive and limiting. Women living with LAM are frustrated by their physical limitations, and they worry about what the future will be like if the disease progresses. Therapeutic interventions should take aim at improving these perceptions.