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While idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias (1), it was once considered a rare, orphan disease. Today, epidemiologic studies suggest that the burden of IPF is considerably greater than previously recognized, and is growing. This highlights the importance of ongoing research into this devastating disease.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by progressive lung scarring and the histological picture of usual interstitial pneumonia (UIP). It is associated with increasing cough and dyspnoea and impaired quality of life. IPF affects ∼3 million people worldwide, with incidence increasing dramatically with age. The diagnostic approach includes the exclusion of other interstitial lung diseases or overlapping conditions and depends on the identification of the UIP pattern, usually with high-resolution CT; lung biopsy might be required in some patients. The UIP pattern is predominantly bilateral, peripheral and with a basal distribution of reticular changes associated with traction bronchiectasis and clusters of subpleural cystic airspaces. The biological processes underlying IPF are thought to reflect an aberrant reparative response to repetitive alveolar epithelial injury in a genetically susceptible ageing individual, although many questions remain on how to define susceptibility. Substantial progress has been made in the understanding of the clinical management of IPF, with the availability of two pharmacotherapeutic agents, pirfenidone and nintedanib, that decrease physiological progression and likely improve progression-free survival. Current efforts are directed at identifying IPF early, potentially relying on combinations of biomarkers that include circulating factors, demographics and imaging data.

RationaleRespiratory-related hospitalizations of patients with idiopathic pulmonary fibrosis (IPF) are more frequent than those for acute IPF exacerbations and are associated with poor outcomes.ObjectivesTo compare the risk of nonelective hospitalization by type (all-cause, respiratory related, and non-respiratory related) and death after hospitalization with use of pirfenidone versus placebo over 52 weeks using data derived from three phase III IPF clinical trials.MethodsIndividual patient data was pooled from three phase III randomized, placebo-controlled studies of pirfenidone for IPF (the two CAPACITY [Clinical Studies Assessing Pirfenidone in IPF: Research of Efficacy and Safety Outcomes] trials and the ASCEND [Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis] trial), including all patients randomized to pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624). The risk of hospitalization over 52 weeks was compared using standard time-to-event methods. Among those hospitalized, the risk of death after hospitalization was compared with adjustment for treatment group propensity.Measurements and main resultsA total of 1,247 patients (692 from the CAPACITY trials and 555 from the ASCEND trial) were included in the pooled analysis. Pirfenidone was associated with lower risk of respiratory-related hospitalization than placebo (7% vs. 12%; hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.77; P = 0.001), but all-cause (HR, 0.91; 95% CI, 0.70-1.19; P = 0.528) or non-respiratory-related hospitalization (HR, 1.32; 95% CI, 0.92-1.88; P = 0.145) was not. Among those hospitalized for any reason, treatment with pirfenidone was associated with lower risk of death after hospitalization up to 52 weeks after randomization, but this association was no longer significant with longer follow-up.ConclusionsIn a pooled analysis of three phase III IPF clinical trials, patients receiving pirfenidone had a lower risk of nonelective respiratory-related hospitalization over the course of 1 year. The effect of pirfenidone on death after hospitalization is uncertain.

Objective.Patients with systemic sclerosis (SSc) often develop interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH). The effect of ILD and PAH on healthcare costs among patients with SSc is not well described. The objective of this analysis was to describe healthcare costs in patients with newly diagnosed SSc and SSc patients newly diagnosed with ILD and/or PAH in the United States.Methods.This retrospective cohort analysis was conducted in the Truven Health MarketScan Commercial and Medicare Supplemental healthcare claims databases from 2003 to 2014. Based on International Classification of Diseases-9-Clinical Modification diagnosis codes on medical claims, patients were classified into 3 groups: incident SSc, SSc with incident ILD (SSc-ILD), and SSc with incident PAH (SSc-PAH). Patients were required to have continuous enrollment for 5 years to measure all-cause healthcare costs. Costs (adjusted to US$) were reported overall and by service type and year following diagnosis. Because of the overlap between groups, statistical comparisons were not conducted.Results.There were 1957 patients with incident SSc, 219 with incident SSc-ILD, and 108 patients with incident SSc-PAH. Average (mean ± SD) all-cause healthcare costs over followup were higher for patients with incident SSc-ILD ($191,107 ± $322,193) or patients with incident SSc-PAH ($254,425 ± $240,497), compared to patients with incident SSc ($101,839 ± $167,155). Average annual costs over the 5-year period ranged from $18,513 to $23,268 for patients with incident SSc, from $31,285 to $55,446 for patients with incident SSc-ILD, and from $44,454 to $63,320 for patients with incident SSc-PAH. Costs tended to be the highest in the fifth year of followup.Conclusion.Among patients with SSc, ILD and PAH can result in substantial increases in healthcare costs.

Background The INSIGHTS-IPF registry provides one of the largest data sets of clinical data and self-reported patient related outcomes including health related quality of life (QoL) on patients with idiopathic pulmonary fibrosis (IPF). We aimed to describe associations of various QoL instruments between each other and with patient characteristics at baseline. Methods Six hundred twenty-three IPF patients with available QoL data (St George’s Respiratory Questionnaire SGRQ, UCSD Shortness-of-Breath Questionnaire SoB, EuroQol visual analogue scale and index EQ-5D, Well-being Index WHO-5) were analysed. Mean age was 69.6 ± 8.7 years, 77% were males, mean disease duration 2.0 ± 3.3 years, FVC pred was 67.5 ± 17.8%, DLCO pred 35.6 ± 17%. Results Mean points were SGRQ total 48.3, UCSD SoB 47.8, EQ-5D VAS 66.8, and WHO-5 13.9. These instruments had a high or very high correlation (exception WHO-5 to EQ-5D VAS with moderate correlation). On bivariate analysis, QoL by SGRQ total was statistically significantly associated with clinical symptoms (NYHA; p

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. Electronic supplementary material The online version of this article (doi:10.1186/s12955-017-0710-0) contains supplementary material, which is available to authorized users.

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

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.

BACKGROUND The usual interstitial pneumonia (UIP) pattern of lung injury may occur in the setting of connective tissue disease (CTD), but it is most commonly found in the absence of a known cause, in the clinical context of idiopathic pulmonary fibrosis (IPF). Our objective was to observe and compare longitudinal changes in pulmonary function and survival between patients with biopsy-proven UIP found in the clinical context of either CTD or IPF. METHODS We used longitudinal data analytic models to compare groups (IPF [n = 321] and CTD-UIP [n = 56]) on % predicted FVC (FVC %) or % predicted diffusing capacity of the lung for carbon monoxide (Dlco%), and we used both unadjusted and multivariable techniques to compare survival between these groups. RESULTS There were no significant differences between groups in longitudinal changes in FVC % or Dlco% up to diagnosis, or from diagnosis to 10 years beyond (over which time, the mean decrease in FVC % per year [95% CI] was 4.1 [3.4, 4.9] for IPF and 3.5 [1.8, 5.1] for CTD-UIP, P = .49 for difference; and the mean decrease in Dlco% per year was 4.7 [4.0, 5.3] for IPF and 4.3 [3.0, 5.6] for CTD-UIP, P = .60 for difference). Despite the lack of differences in pulmonary function, subjects with IPF had worse survival in unadjusted (log-rank P = .003) and certain multivariable analyses. CONCLUSIONS Despite no significant differences in changes in pulmonary function over time, patients with CTD-UIP (at least those with certain classifiable CTDs) live longer than patients with IPF—an observation that we suspect is due to an increased rate of mortal acute exacerbations in patients with IPF.

For patients with idiopathic pulmonary fibrosis (IPF), prognosis is extremely poor and treatment options are limited. An improved understanding of the experiences and expectations of IPF patients could lead to better clinical management and patient satisfaction. A review of the literature found that diagnosis of IPF typically involved a protracted course including multiple evaluations. Patients felt that educational resources were inadequate and inaccessible. Overall, patients had reasonable expectations for IPF-specific therapies, and were enthusiastic about trying promising new therapies. Numerous domains of health and functioning identified by patients as important were impaired because of IPF. Existing patient-reported outcome instruments (including assessments of health-related quality of life) do not capture many of these domains or are irrelevant to patients with IPF, highlighting the need for an IPF-specific instrument. Patients treated in centers of excellence expressed greater satisfaction with quality of care and treatments, and also valued the opportunity to interact with other IPF patients.

SummaryBackgroundDyspnea is a hallmark symptom of idiopathic pulmonary fibrosis (IPF), and dyspnea induced physical activity limitation is a prominent driver of quality of life impairment among IPF patients.MethodsWe examined response data for the 21 physical activity items (the first 21 of 24) from the University of California San Diego Shortness of Breath Questionnaire (UCSD) collected at baseline in a recently conducted IPF trial. We used Rasch analysis and hypothesis testing with conventional statistical methodology to achieve three objectives: 1) to examine the items to identify the one characteristic that distinguishes one from another; 2) to asses these items for their ability to measure dyspnea severity in IPF; 3) to use the items to develop a dyspnea ruler.ResultsThe sample comprised 178 subjects. The 21 items fit the Rasch model. There was very strong correlation between Rasch item severity and their metabolic equivalents (METS) values (r = −0.86, p

Over the past decade, it has been increasingly recognized that patients with idiopathic pulmonary fibrosis (IPF) are at risk of both venous thromboembolic disease (VTE) and coronary artery disease (CAD). When present, these co-morbid conditions negatively affect outcomes. For this disease without effective therapy to improve survival, increased diagnosis and treatment of these co-morbid processes may improve outcomes. Better understanding of the mechanisms that place IPF patients at increased risk of VTE and CAD may also ultimately lead to novel therapeutic interventions.

Purpose of review To summarize current knowledge of health-related quality of life (HRQL) assessment in idiopathic pulmonary fibrosis (IPF), with an emphasis on reviewing available data on HRQL instruments, operationalizing HRQL assessment in IPF research and interventions that show promise for improving HRQL in patients with IPF. Recent findings Findings from several studies support the validity of the Medical Outcomes Study Short-Form 36-item Questionnaire and St George's Respiratory Questionnaire for assessing HRQL in IPF. IPF-specific HRQL instruments are in development, but additional research is needed before their broad implementation. Pulmonary rehabilitation and IPF disease management programs appear to be promising interventions for improving HRQL in IPF patients. Summary IPF is a devastating disease. Because there is no cure, an improved understanding of how this disease affects patients' lives is needed. Rigorously developed and carefully administered instruments are needed to assess those effects and to measure the impact of interventions aimed at improving the lives of patients with IPF.

SummaryBackgroundVEGF-D is a lymphangiogenic growth factor that has a key role in tumour metastasis. Serum VEGF-D concentrations are increased in most patients with lymphangioleiomyomatosis, a rare neoplasm associated with mTOR-activating tuberous sclerosis gene mutations, lymphadenopathy, metastatic spread, and pulmonary cyst formation. We used data from the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial to assess the usefulness of serum VEGF-D concentration as a marker of severity and therapeutic response to sirolimus in patients with lymphangioleiomyomatosis.MethodsIn the MILES trial, patients with lymphangioleiomyomatosis who had forced expiratory volume in 1 second (FEV1) of 70% or less of predicted were randomly assigned (1:1) to 12 months masked treatment with sirolimus or placebo. Serum VEGF-D concentrations were measured at baseline, 6 months, and 12 months. We used a linear regression model to assess associations of baseline VEGF-D concentrations with markers of disease severity, and a linear mixed effects model to assess the associations of VEGF-D concentrations with between-group differences in clinical, physiological, and patient-reported outcomes.FindingsWe included 42 patients from the placebo group and 45 from the sirolimus group in our analysis. Baseline VEGF-D concentrations in individual patients varied from 0·34 ng/mL to 16·7 ng/mL. Baseline VEGF-D concentrations were higher in patients who needed supplemental oxygen than in those who did not need supplemental oxygen (1·7 ng/mL [IQR 0·99–3·36] vs 0·84 ng/mL [0·52–1·39]; p

Summary Background Fibrosis or inflammation of the bronchioles is a well-known manifestation of connective tissue disease (CTD). However, the natural history of CTD-related bronchiolitis is largely unknown. Methods We analyzed consecutive patients evaluated at National Jewish Health (Denver, CO) from 1998 to 2008 with CTD and surgical lung biopsy-confirmed bronchiolitis. Linear mixed effects models were used to estimate the longitudinal postbronchodilator FEV 1 %predicted (%pred) course and differences between subjects with or without constrictive bronchiolitis (CB). Results Of 28 subjects with a mean age of 53 ± 9 years, fourteen (50%) had CB. The most common CTD diagnosis was rheumatoid arthritis ( n = 14; 50%). There were no significant differences in demographics, smoking status, underlying CTD diagnoses, 6-min walk distance, dyspnea score or drug therapy between subjects with CB and those with cellular bronchiolitis. Three subjects with CB (11%) and four with cellular bronchiolitis (14%) died. Compared with subjects with CB, those with cellular bronchiolitis had higher mean FEV 1 %pred at all times. There were no significant differences in FEV 1 %pred slope within- or between-groups (CB vs. cellular bronchiolitis) preceding surgical lung biopsy or afterward. Conclusion Subjects with CTD-related CB had lower FEV 1 %pred values than those with CTD-related cellular bronchiolitis at all time points, but FEV 1 %pred remained stable over time in both groups regardless of therapy received.

Summary Background In clinical trials of idiopathic pulmonary fibrosis, rates of all-cause mortality are low. Thus prospective mortality trials are logistically very challenging, justifying the use of pooled analyses or meta-analyses. We did pooled analyses and meta-analyses of clinical trials of pirfenidone versus placebo to determine the effect of pirfenidone on mortality outcomes over 120 weeks. Methods We did a pooled analysis of the combined patient populations of the three global randomised phase 3 trials of pirfenidone versus placebo—Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY 004 and 006; trial durations 72–120 weeks) and Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND 016; 52 weeks)—for all-cause mortality, treatment-emergent all-cause mortality, idiopathic-pulmonary-fibrosis-related mortality, and treatment-emergent idiopathic-pulmonary-fibrosis-related mortality at weeks 52, 72, and 120. We also did meta-analyses of these data and data from two Japanese trials of pirfenidone versus placebo—Shionogi Phase 2 (SP2) and Shionogi Phase 3 (SP3; trial durations 36–52 weeks). Findings At week 52, the relative risk of death for all four mortality outcomes was significantly lower in the pirfenidone group than in the placebo group in the pooled population (all-cause mortality hazard ratio [HR] 0·52 [95% CI 0·31–0·87; p=0·0107]; treatment-emergent all-cause mortality 0·45 [0·24–0·83; 0·0094]; idiopathic-pulmonary-fibrosis-related mortality 0·35 [0·17–0·72; 0·0029]; treatment-emergent idiopathic-pulmonary-fibrosis-related mortality 0·32 [0·14–0·76; 0·0061]). Consistent with the pooled analysis, meta-analyses for all-cause mortality at week 52 also showed a clinically relevant and significant risk reduction in the pirfenidone group compared with the placebo group. Over 120 weeks, we noted significant differences in the pooled analysis favouring pirfenidone therapy compared with placebo for treatment-emergent all-cause mortality (p=0·0420), idiopathic-pulmonary-fibrosis-related mortality (0·0237), and treatment-emergent idiopathic-pulmonary-fibrosis-related (0·0132) mortality; similar results were shown by meta-analyses. Interpretation Several analytic approaches demonstrated that pirfenidone therapy is associated with a reduction in the relative risk of mortality compared with placebo over 120 weeks. Funding F Hoffmann-La Roche/Genentech.

Background: Health-related quality of life (HRQL) is impaired among patients with interstitial lung disease (ILD). Less is understood about HRQL in specific subtypes of ILD. The aim of this study was to characterize HRQL among patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) compared to patients with idiopathic pulmonary fibrosis (IPF) and …

Purpose: To determine which clinical, radiologic, or histopathologic characteristics might predict which patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP) go on to develop rheumatoid arthritis (UIP/pre-RA). Methods: We reviewed the records of 74 patients (IPF/UIP, 63; UIP/pre-RA, 11) with UIP-pattern identified in surgical lung biopsy specimens. For the study, chest CT and histopathology slides were re-reviewed by two expert pulmonary radiologists and pathologists respectively. Results: The median follow up period was 4.2 years. In patients with UIP/pre-RA, mean duration from UIP diagnosis to RA development was 0.9 years. There were no significant differences in clinical features or CT findings between two groups. UIP/pre-RA group was more likely to have higher pO 2 (p=0.009), rheumatoid factor, anti-cyclic citrullinated peptide antibody (p Conclusions: Clinical and radiologic features of UIP/pre-RA were similar to those seen in IPF/UIP. The fibrobrastic foci score and germinal centers score were the best discriminative between IPF/UIP and UIP/pre-RA patients. In patients with IPF/UIP and a low fibrobrastic foci score and high germinal center score on biopsy, there is a risk of development of RA in the future.

Background: Pirfenidone has been shown to decrease the annual rate of decline in forced vital capacity (FVC) volume in patients with idiopathic pulmonary fibrosis (IPF). This analysis explored this effect in various patient subgroups. Methods: Patients randomized to pirfenidone 2403 mg/d or placebo in the CAPACITY or ASCEND studies were included. The annualized rate of decline in FVC volume from baseline through 12 months was estimated using a mixed-effects model, with study, time-by-treatment, age-by-sex and height-by-sex as fixed effects and patients and time-by-patient (slope) as random effects. The annual rate of FVC decline was estimated from the slope within the subgroups, defined by demographics and baseline disease activity measures. Results: A total of 623 patients in the pirfenidone group and 624 in the placebo group were included in the pooled analysis. Overall, the adjusted annual rate (SE) of FVC decline from baseline to 12 months was −109.0 (13.6) mL for pirfenidone vs −207.5 (13.7) mL for placebo, a difference of 98.5 (17.5) mL. The annual rate of FVC decline favored pirfenidone over placebo across various baseline demographic and lung function subgroups (Figure). Conclusions: Patients with IPF treated with pirfenidone, regardless of baseline demographic or lung function, had a significantly lower annual rate of decline in FVC volume vs those treated with placebo after 12 months.

Background: Previous analyses of patients with IPF receiving pirfenidone showed that continued treatment following a ≥ 10% absolute or relative decline in percent predicted forced vital capacity (FVC) or hospitalization during the first 6 months of treatment provided a benefit during the subsequent 6 months. Objective: To further explore the potential benefit of continued pirfenidone treatment in patients with IPF who had a worsening of 6MWD within the first 6 months of treatment. Methods: A pooled analysis included all patients randomized to pirfenidone 2403 mg/d or placebo in the ASCEND and CAPACITY studies (N = 1247). All patients who had a 6MWD decline ≥ 15% within the first 6 months of study treatment were selected. FVC, 6MWD, mortality and hospitalization outcomes were assessed during the subsequent 6-month period. Results: A total of 116/623 (18.6%) and 141/624 (22.6%) patients in the pooled pirfenidone and placebo groups, respectively, demonstrated a 6MWD decline ≥ 15% within the first 6 months of treatment. Outcomes during the subsequent 6 months of continued treatment in these patients are shown in the Table. Conclusions: These results suggest that continued treatment with pirfenidone may confer a significant benefit to patients with IPF who experienced a 6MWD decline ≥ 15% within the first 6 months of treatment.

Introduction: Pulmonary hypertension (PH) is a potentially severe complication of interstitial lung disease (ILD) that results from multiple mechanisms, including hypoxic pulmonary vasoconstriction. Because hyperoxia may have vasodilatory effects, we tested whether acute hyperoxia improved hemodynamics and pulmonary vascular stiffness in an ILD-PH cohort. Methods: Patients with ILD and suspected PH underwent right heart catheterization (RHC). Patients with low peripheral oxygen saturation (SpO 2 ) were administered supplemental O 2 to achieve an SpO 2 ≥ 90% and then haemodynamic data were collected. Hemodynamics were repeated after 100% FiO 2 for 5 minutes. Results: The cohort comprised 23 patients with ILD and RHC-proven PH (mean pulmonary artery pressure (mPAP) 33±7.34 mmHg, pulmonary artery occlusion pressure 12±2.5 mmHg, pulmonary vascular resistance (PVR) 4.9±2.8 Wood9s Units (WU), and capacitance 2.07±0.89 mL/mmHg. 11 patients required supplemental oxygen to achieve an SpO 2 >90% The baseline mean SpO 2 was 94.4%; 3 patients were hypoxic (PaO 2 2 improved SpO 2 (+4.1%), reduced mPAP (-2.7±4.3 mmHg, p=0.002), PVR (-0.78±1.24 WU, p=0.0007), and pulmonary vascular stiffness (increased capacitance) (+0.39±0.48 mmHg/mL, p Discussion: Hyperoxia acutely improves hemodynamics and vascular stiffness even in the absence of hypoxaemia, suggesting oxygen supplementation may be beneficial in normoxic ILD PH. Because proximal pulmonary arterial remodeling contributes significantly to overall vascular stiffness, these acute changes in stiffness with hyperoxia suggest previously undescribed improvements in proximal arterial mechanics.

Background: During treatment of idiopathic pulmonary fibrosis with pirfenidone (PFD), gastrointestinal and skin-related adverse drug reactions (ADR) occurred in ∼30% of patients (pts). Temporary dose reductions and interruptions may allow pts to better manage side effects and continue PFD. Objective: To evaluate PFD reductions and interruptions in the Phase 3 CAPACITY and ASCEND trials. Methods: Pts (623 PFD 2403 mg/day, 624 placebo [PBO]) were followed over 52 weeks. Descriptive statistics and a linear slope analysis for annual rate of decline in forced vital capacity (FVC) by dose intensity were performed. Results: Mean daily dose was 2105 mg (median, 2300 mg). Dose reductions and interruptions occurred in 46% and 41% of PFD pts vs 29% and 25% of PBO pts, respectively. Median duration of reductions and interruptions for PFD pts were 28 and 14 days, respectively. Median time from start of PFD to first dose adjustment for common AEs was ∼95 days except for vomiting (28 days). Dose intensity of >90% was observed in 424/623 PFD and 559/624 PBO pts. The mean difference (±SEM) in annual rate of FVC decline between PFD and PBO over 52 weeks was 105.5±18.4 mL for dose intensity >90% (P Conclusions: While PFD dose adjustments may be required to manage ADRs, they tended to occur early and were limited in duration, allowing most pts to maintain efficacy and a high dose intensity.

RationaleHealth-related quality of life (HRQL) is impaired among patients with interstitial lung disease (ILD). Little is understood about HRQL in specific subtypes of ILD.ObjectivesThe aim of this study was to characterize and identify clinical determinants of HRQL among patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and compare them to patients with idiopathic pulmonary fibrosis (IPF).MethodsWe identified patients with a diagnosis of RA-ILD and IPF from an ongoing longitudinal cohort of ILD patients. HRQL was measured at their baseline visit using the Short Form Health Survey (SF-36), versions 1 and 2. Regression models were used to characterize and understand the relationship between selected baseline clinical covariates, the physical component score (PCS) and mental component score (MCS) of the SF-36.Measurements and main resultsRA-ILD patients (n=50) were more likely to be younger and female compared to IPF patients (n=50). After controlling for age and pulmonary function, RA-ILD patients had a lower HRQL compared to IPF patients, as measured by the PCS (P=0.03), with significant differences in two of four PCS domains - bodily pain (P&nbsp

Objective To describe the clinical phenotype and natural history of a cohort of patients with interstitial pneumonia with autoimmune features (IPAF). Methods A retrospective, single center study of 56 patients with IPAF evaluated between February 2008 and August 2014. All clinical data were extracted from the electronic medical record and longitudinal changes in forced vital capacity (FVC) were analyzed with mixed-effects, piecewise linear regression models that considered time as a continuous factor. Results All patients fulfilled classification criteria for IPAF. The majority were women (71%) and never smokers (68%). The most frequently identified clinical features were Raynaud's phenomenon (39%), distal digital fissuring (29%), Gottron's sign (18%) and inflammatory arthropathy (16%). The most frequently identified serologies were antinuclear antibody (ANA) (48%), anti-Ro (SSA) (43%) and anti-tRNA-synthetase antibodies (36%). Nonspecific interstitial pneumonia (NSIP) (57.1%) followed by NSIP with organizing pneumonia (18%) were the most common radiologic patterns, while usual interstitial pneumonia was identified in only 9%. All but one patient was treated with immunosuppression: prednisone (82%) and mycophenolate mofetil (76%) were the most frequently used agents. During a follow-up period of 284.9 ± 141.3 days, modeled longitudinal FVC% was stable (slope = 0.69/year) and no deaths were observed in the cohort. Conclusions In this single center study, patients with IPAF were predominately non-smoking women with high-resolution computed tomography scans that suggested NSIP. Their pulmonary physiology was stable, and during limited follow-up, no deaths were observed. Prospective and multi-center studies are needed to better inform our understanding of IPAF.

Summary Background 12 months of oral cyclophosphamide has been shown to alter the progression of scleroderma-related interstitial lung disease when compared with placebo. However, toxicity was a concern and without continued treatment the efficacy disappeared by 24 months. We hypothesised that a 2 year course of mycophenolate mofetil would be safer, better tolerated, and produce longer lasting improvements than cyclophosphamide. Methods This randomised, double-blind, parallel group trial enrolled patients from 14 US medical centres with scleroderma-related interstitial lung disease meeting defined dyspnoea, pulmonary function, and high-resolution CT (HRCT) criteria. The data coordinating centre at the University of California, Los Angeles (UCLA, CA, USA), randomly assigned patients using a double-blind, double-dummy, centre-blocked design to receive either mycophenolate mofetil (target dose 1500 mg twice daily) for 24 months or oral cyclophosphamide (target dose 2·0 mg/kg per day) for 12 months followed by placebo for 12 months. Drugs were given in matching 250 mg gel capsules. The primary endpoint, change in forced vital capacity as a percentage of the predicted normal value (FVC %) over the course of 24 months, was assessed in a modified intention-to-treat analysis using an inferential joint model combining a mixed-effects model for longitudinal outcomes and a survival model to handle non-ignorable missing data. The study was registered with ClinicalTrials.gov, number NCT00883129. Findings Between Sept 28, 2009, and Jan 14, 2013, 142 patients were randomly assigned to either mycophenolate mofetil (n=69) or cyclophosphamide (n=73). 126 patients (mycophenolate mofetil [n=63] and cyclophosphamide [n=63]) with acceptable baseline HRCT studies and at least one outcome measure were included in the primary analysis. The adjusted % predicted FVC improved from baseline to 24 months by 2·19 in the mycophenolate mofetil group (95% CI 0·53–3·84) and 2·88 in the cyclophosphamide group (1·19–4·58). The course of the % FVC did not differ significantly between the two treatment groups based on the prespecified primary analysis using a joint model (p=0·24), indicating that the trial was negative for the primary endpoint. However, in a post-hoc analysis of the primary endpoint, the within-treatment change from baseline to 24 months derived from the joint model showed that the % FVC improved significantly in both the mycophenolate mofetil and cyclophosphamide groups. 16 (11%) patients died (five [7%] mycophenolate mofetil and 11 [15%] cyclophosphamide), with most due to progressive interstitial lung disease. Leucopenia (30 patients vs four patients) and thrombocytopenia (four vs zero) occurred more often in patients given cyclophosphamide than mycophenolate mofetil. Fewer patients on mycophenolate mofetil than on cyclophosphamide prematurely withdrew from study drug (20 vs 32) or met prespecified criteria for treatment failure (zero vs two). The time to stopping treatment was shorter in the cyclophosphamide group (p=0·019). Interpretation Treatment of scleroderma-related interstitial lung disease with mycophenolate mofetil for 2 years or cyclophosphamide for 1 year both resulted in significant improvements in prespecified measures of lung function over the 2 year course of the study. Although mycophenolate mofetil was better tolerated and associated with less toxicity, the hypothesis that it would have greater efficacy at 24 months than cyclophosphamide was not confirmed. These findings support the potential clinical effectiveness of both cyclophosphamide and mycophenolate mofetil for progressive scleroderma-related interstitial lung disease, and the present preference for mycophenolate mofetil because of its better tolerability and toxicity profile. Funding National Heart, Lung and Blood Institute, National Institutes of Health; with drug supply provided by Hoffmann-La Roche and Genentech.

Granulomatous-lymphocytic interstitial lung disease (GLILD) has emerged as a major cause of morbidity in patients with common variable immunodeficiency (CVID). While GLILD is among the most serious noninfectious pulmonary complications of CVID, risk factors for this condition have not been reported.To identify clinical, physiologic, and serologic risk factors for GLILD in adults with CVID.Of 345 consecutive adult patients with CVID, we identified 34 in the National Jewish Health research database who had a radiographic-pathologic diagnosis of GLILD evaluated between 2002 and 2014. Each case was age and sex matched to 52 CVID control subjects. We used logistic regression to determine independent predictors of GLILD. A mixed effects model was used to estimate the longitudinal change in percent predicted FVC.The mean time from CVID diagnosis to GLILD detection was 7.8 years. Compared with matched control subjects, cases were more likely to have a history of autoimmune cytopenia, hypersplenism, polyarthritis, lower marginal zone and switched memory B cells, and restrictive lung function. Multivariate analysis revealed that hypersplenism (odds ratio [OR], 24; 95% confidence interval [CI], 4.5-179.1), polyarthritis (OR, 19; 95% CI, 2.3-206.8), and percent predicted FVC (OR, 0.93; 95% CI, 0.87-0.98) were independently associated with the development of GLILD. The rate of change of percent predicted FVC (slope, P = 0.48) did not vary significantly in patients with GLILD over a mean follow-up of 7 years after diagnosis.Hypersplenism and polyarthritis are strong risk factors for GLILD in patients with CVID. Percent predicted FVC remained stable over time in patients with GLILD.

SummaryBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that often causes disabling dyspnea. In IPF and other lung diseases, patient-reported outcomes (PROs)—questionnaires designed to gather information from the patient's perspective—can determine whether therapies affect dyspnea or other outcomes meaningful to patients. Before a PRO can be used confidently as an outcome measure in a longitudinal trial, studies must demonstrate the PRO's ability to capture change over time in the target population. Our goal in this study was to examine whether the UCSD Shortness of Breath Questionnaire does so in patients with IPF.MethodsWe used data from the Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF) to perform analyses that examined associations between UCSD scores and five external measures (anchors) at baseline and over time. Anchors included the Activity domain from St. George's Respiratory Questionnaire (SGRQ-A), the Physical Functioning domain from the SF-36 (SF36-PF), forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and distance walked during a timed walk test (6MWD). Linear regression models were used to examine relationships between UCSD scores and anchors over time.ResultsAt baseline, UCSD scores were weakly correlated with percent predicted FVC (−0.21, p = 0.005) and percent predicted DLCO (−0.20, p = 0.008), moderately correlated with 6MWD (−0.39, p

Interstitial lung disease (ILD) is commonly encountered in patients with connective tissue diseases (CTD). Besides the lung parenchyma, the airways, pulmonary vasculature and structures of the chest wall may all be involved, depending on the type of CTD. As a result of this so-called multi-compartment involvement, airflow limitation, pulmonary hypertension, vasculitis and extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal abnormalities in CTD. Rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), Sjogren’s syndrome (SjS), systemic lupus erythematosus (SLE), and undifferentiated connective tissue disease (UCTD), as well as mixed connective tissue disease (MCTD), can all be associated with the development of ILD. Nonspecific interstitial pneumonia (NSIP) is the most commonly observed histopathological pattern in CTD-ILD, but other patterns, including usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP), may occur. Although the majority of patients with CTD-ILD experience stable or slowly advancing ILD, a small yet significant group exhibits a more severe and progressive course. Randomized placebo-controlled trials evaluating the efficacy of immunomodulatory treatments have been conducted only in SSc-associated ILD. However, clinical experience suggests that a handful of immunosuppressive medications are potentially effective in a sizeable portion of patients with ILD caused by other CTDs. In this manuscript, we review the clinical characteristics and management of the most common CTD-ILDs.

Patient-reported outcomes (PROs) include questionnaires or surveys that ask patients for their perceptions about things like symptoms they are experiencing or quality of life. For incurable, morbid, life-shortening conditions like idiopathic pulmonary fibrosis (IPF), PROs are particularly germane: They elucidate for clinicians and researchers what it is like for patients to live with such a disease, and they may detect important treatment effects not captured by other metrics (eg, pulmonary physiology). However, a relative paucity of research on PROs in IPF has left significant knowledge gaps in this area and contributed to the timidity investigators have about using PROs as prominent outcomes in IPF drug trials. Additional research on existing instruments is needed to establish or bolster their basic psychometric properties in IPF. When PROs are used as end points in therapeutic trials, analyzing PRO response data can be challenging, but these challenges can be overcome with a transparent, thoughtful, and sophisticated statistical approach. In this article, we discuss some of the basics of PRO assessment, existing knowledge gaps in IPF-related PRO research, and the potential usefulness of using PROs in IPF trials and conclude by offering specific recommendations for an approach to analyzing repeated-measures PRO data from IPF trials.

Summary Objective We sought to characterize a novel cohort of patients with lung disease, anti-cyclic citrullinated peptide (CCP) antibody positivity, without rheumatoid arthritis (RA) or other connective tissue disease (CTD). Methods The study sample included 74 subjects with respiratory symptoms, evaluated January 2008–January 2010 and found to have a positive anti-CCP antibody but no evidence for RA or other CTD. Each underwent serologic testing, pulmonary physiology testing, and thoracic high-resolution computed tomography (HRCT) scan as part of routine clinical evaluation. Results The majority of subjects were women, and most were former cigarette smokers. Four distinct radiographic phenotypes were identified: isolated airways disease (54%), isolated interstitial lung disease (ILD) (14%), mixed airways disease and ILD (26%), and combined pulmonary fibrosis with emphysema (7%). This cohort had a predominance of airways disease, either in isolation or along with a usual interstitial pneumonia-pattern of ILD. Among subjects with high-titer anti-CCP positivity ( n =33), three developed the articular manifestations of RA during a median follow-up of 449 days. Conclusion We have described a unique cohort of patients with anti-CCP antibody positivity and lung disease in the absence of existing RA or other CTD. The lung phenotypic characteristics of this cohort resemble those of established RA and a few of these patients have developed articular RA within a short period of follow-up. The implications of a positive anti-CCP antibody among patients with lung disease but not RA are not yet known, but we believe requires further investigation.

Idiopathic pulmonary fibrosis (IPF) is a dreadful disease that lacks adequate therapy. A number of treatment trials have been performed and have utilized a variety of primary efficacy endpoints. Endpoints that provide the most useful efficacy information are clinical endpoints that are directly related to how a patient feels, functions or survives. Unfortunately, there are no properly established patient-reported outcome measures or measures of functional status in IPF, making survival the most robust primary efficacy endpoint. Clinically meaningful events such as hospitalization can also provide important efficacy information. The use of non-validated surrogate endpoints as primary outcome measures often leads to uncertainty when interpreting trial results.

A recently published report from the United Kingdom suggested an association between sarcoidosis and pulmonary embolism (PE). We sought to examine whether this association was present among US decedents with sarcoidosis.We used data from the National Center for Health Statistics to investigate the association between sarcoidosis and PE among US decedents from 1988 to 2007.From 1988 to 2007, there were 46,450,489 deaths in the United States and 23,679 decedents with sarcoidosis mentioned on their death certificates. Among these, 602 (2.54%) had PE mentioned on their death certificates, compared with only 1.13% of the background population (P.0001 for comparison). The association between sarcoidosis and PE was significant regardless of gender (OR, 2.07; 95% CI, 1.80-2.39; P.0001 for men and OR, 1.76; 95% CI, 1.59-1.96; P ≤ .0001 for women) or race (OR, 1.57; 95% CI, 1.41-1.76; P.0001 for blacks and OR, 1.87; 95% CI, 1.63-2.14; P.0001 for whites). Among decedents with sarcoidosis, there was no difference in risk of PE between men and women (2.30% vs 2.54%, χ(2) = 1.32, P = .25) or between blacks and whites (2.60% vs 2.23%, χ(2) = 3.09, P = .08). The association between sarcoidosis and PE held regardless of age.Using death certificate data from 1988 to 2007, we detected an association between sarcoidosis and PE regardless of gender, race, or age. Further investigation is needed to decipher the mechanisms of this apparent association.

Recent epidemiological studies have suggested an increased risk of venous thromboembolism (VTE) in lung fibrosis. Large-scale epidemiological data regarding the risk of VTE in pulmonary fibrosis-associated mortality have not been published. Using data from the National Center for Health Statistics from 1988-2007, we determined the risk of VTE in decedents with pulmonary fibrosis in the USA. We analysed 46,450,489 records, of which 218,991 met our criteria for idiopathic pulmonary fibrosis. Among these, 3,815 (1.74%) records also contained a diagnostic code for VTE. The risk of VTE in pulmonary fibrosis decedents was 34% higher than in the background population, and 44% and 54% greater than among decedents with chronic obstructive pulmonary disease and lung cancer, respectively. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone (females: 74.3 versus 77.4 yrs (p

Dyspnea is a prominent symptom in asthma. The Dyspnea-12 (D-12), an instrument that quantifies breathlessness using 12 descriptors that tap the physical and affective aspects, has shown promise for the measurement of dyspnea in cardiorespiratory disease.We report the results of a study designed to test the validity and reliability of the D-12 in a population of patients with asthma.This cross-sectional study included 102 patients with asthma. Subjects completed the D-12, Hospital Anxiety and Depression scale, St. George's Respiratory Questionnaire (SGRQ), and Medical Research Council scale. Confirmatory factor analysis confirmed the two-component structure of the D-12 (i.e., seven items that tap the physical aspects of breathlessness and five items that tap the affective aspects).The D-12 subscales had excellent internal reliability (Cronbach's alpha for the "physical" score was 0.94 and the affective score was 0.95). The D-12 physical component was more strongly correlated with SGRQ Symptoms (r = 0.648), SGRQ Activities (r = 0.635) and Medical Research Council grade (r = 0.636), while the affective component was more strongly correlated with SGRQ Impacts (r = 0.765) and Hospital Anxiety and Depression scale scores (anxiety r = 0.641 and depression r = 0.602).This study supports validity of the D-12 for use in the assessment of dyspnea of patients with asthma. It assesses one of the most pertinent symptoms of asthma from two viewpoints-physical and affective.

Rationale: It has been nearly 20 years since sarcoidosis mortality was examined at the population level in the United States.Objectives: To examine mortality rates and underlying causes of death among United States decedents with sarcoidosis from 1988–2007.Methods: We used data from the National Center for Health Statistics to (1) calculate age-adjusted sarcoidosis-associated mortality rates; (2) examine how those rates differ by age, sex, and race and ethnicity; and (3) determine underlying causes of death among sarcoidosis decedents.Measurements and Main Results: From 1988–2007, there were 46,450,489 deaths in the United States and 23,679 decedents with sarcoidosis mentioned on their death certificates. Over this time, the age-adjusted, sarcoidosis-related mortality rate increased 50.5% in women and 30.1% in men. The greatest absolute increase in death rates was among non-Hispanic black females. Regardless of sex or race, mortality rates climbed most in decedents 55 years or older. The most common cause...

Background and objective In patients with IPF, we sought to validate that abnormal heart rate recovery at 1 min (HRR1) after six-minute walk test (6MWT) predicts mortality and to explore the relationship between abnormal HRR1 and pulmonary hypertension (PH).

Mortality rates from rheumatoid arthritis-associated interstitial lung disease (RA-ILD) are largely unknown.We sought to determine mortality rates from rheumatoid arthritis-associated interstitial lung disease in the United States from 1988 through 2004.Using data from the National Center for Health Statistics, we calculated age-adjusted mortality rates from the deaths of persons with rheumatoid arthritis-associated interstitial lung disease, determined the prevalence of interstitial lung disease in all decedents with rheumatoid arthritis, and compared the age and underlying cause of death in these two cohorts of decedents.From 1988 to 2004, there were 39,138,394 deaths in U.S. residents and 162,032 rheumatoid arthritis-associated deaths. Of these deaths, 10,725 (6.6%) met criteria for rheumatoid arthritis-associated interstitial lung. Mortality rates from rheumatoid arthritis fell over the course of this study in both women and men. However, mortality rates from rheumatoid arthritis-associated interstitial lung disease increased 28.3% in women (to 3.1 per million persons in 2004) and declined 12.5% in men (to 1.5 per million persons in 2004). Because the rate of decline in rheumatoid arthritis outpaced rheumatoid arthritis-associated interstitial lung disease in men, the prevalence of rheumatoid arthritis-associated interstitial lung disease increased in both sexes over time.Clinically significant RA-ILD occurs in nearly 10% of the RA population, and is associated with shortened survival and more severe underlying disease. Whereas overall mortality rates for RA have fallen, those associated with RA-ILD have increased significantly in older age groups.

Em pacientes com miosite, é comum o comprometimento pulmonar, e a presença de anticorpos anti-aminoacil-RNAt sintetase (anti-ARS) é preditora da presença ou do desenvolvimento de doença pulmonar intersticial (DPI). Uma entidade clínica distinta - a síndrome antissintetase - é caracterizada pela presença de anticorpos anti-ARS, miosite, DPI, artrite, fenômeno de Raynaud e "mãos de mecânico". O mais comum anticorpo anti-ARS é o anti-Jo-1. Anticorpos anti-ARS mais recentemente descritos podem conferir um fenótipo que é distinto daquele de pacientes com positividade para anti-Jo-1, sendo caracterizado por uma menor incidência de miosite e uma maior incidência de DPI. Nos pacientes com DPI relacionada à síndrome antissintetase, a resposta a medicações imunossupressoras é em geral favorável.In patients with myositis, the lung is commonly involved, and the presence of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies marks the presence or predicts the development of interstitial lung disease (ILD). A distinct clinical entity-antisynthetase syndrome-is characterized by the presence of anti-ARS antibodies, myositis, ILD, fever, arthritis, Raynaud's phenomenon, and mechanic's hands. The most common anti-ARS antibody is anti-Jo-1. More recently described anti-ARS antibodies might confer a phenotype that is distinct from that of anti-Jo-1-positive patients and is characterized by a lower incidence of myositis and a higher incidence of ILD. Among patients with antisynthetase syndrome-related ILD, the response to immunosuppressive medications is generally, but not universally, favorable.

In this study, we aimed to determine the validity and reliability of the Dyspnea-12 questionnaire (D-12) for the assessment of breathlessness in patients with interstitial lung disease (ILD).A total of 101 patients with ILD completed the D-12 (scale range, 0-36, with a high score indicating worse dyspnea), Medical Research Council (MRC) dyspnea scale, St. George Respiratory Questionnaire (SGRQ), and Hospital Anxiety and Depression Scale (HADS) at baseline, and 84 patients completed the D-12 and a global health transition score at follow-up 2 weeks later. D-12 psychometric properties, including floor and ceiling effects, internal consistency, test-retest reliability, and construct validity were examined.The D-12 showed good internal consistency (Cronbach α, 0.93) and repeatability (intraclass correlation coefficient, 0.94). Its scores were significantly associated with MRC grade (r = 0.59; P.001), SGRQ (symptoms, r = 0.57; activities, r = 0.78; impacts, r = 0.75; total, r = 0.79; P.001). Factor analysis confirmed the previously determined structure of the D-12 in this patient group.In patients with ILD, the D-12, a patient-reported measure of dyspnea severity that requires no reference to activity, is a reliable and valid instrument. It is short, simple to complete, and easy to score.

The effects of interstitial lung disease (ILD) create a significant burden on patients, unsettling almost every domain of their lives, disrupting their physical and emotional well-being and impairing their quality of life (QoL). Because many ILDs are incurable, and there are limited reliably-effective, life-prolonging treatment options available, the focus of many therapeutic interventions has been on improving or maintaining how patients with ILD feel and function, and by extension, their QoL. Such patient-centred outcomes are best assessed by patients themselves through tools that capture their perceptions, which inherently incorporate their values and judgements. These patient-reported outcome measures (PROs) can be used to assess an array of constructs affected by a disease or the interventions implemented to treat it. Here, we review the impact of ILD that may present with a progressive-fibrosing phenotype on patients' lives and examine how PROs have been used to measure that impact and the effectiveness of therapeutic interventions.

Rationale The St George's Respiratory Questionnaire (SGRQ) is often applied to assess health-related quality of life in patients with idiopathic pulmonary fibrosis (IPF). Some SGRQ items will inevitably have weaker measurement properties than others when applied to this population. This study was conducted to develop an IPF-specific version of the SGRQ.\ud \ud Methods Data from a recently completed trial that enrolled subjects with IPF (n=158) who completed the SGRQ and other measures were analysed at baseline and 6 months. There were four phases to the study: (1) removing items with missing responses and using Rasch analysis on retained items to identify fit and refine item response categories; (2) development of a new scoring scheme; (3) testing agreement between original and revised versions and testing construct validity of the revised SGRQ; and (4) rewording to finalise the IPF-specific version (SGRQ-I).\ud \ud Results Items were removed due to missing responses (6 items) and misfit to the Rasch model (10 items); 34 items from the original 50 were retained. For certain items, disordered response thresholds were identified and corrected by collapsing response categories. A scoring algorithm was developed to place SGRQ-I scores on a scale with SGRQ scores. For any given outcome measure (eg, forced vital capacity (% predicted) and lung carbon monoxide transfer factor (% predicted), 6-min walk distance and patient-reported questionnaires), Pearson correlations were similar between pairs that included original SGRQ scores and corresponding pairs that included SGRQ-I scores. Internal reliability (Cronbach α) for each SGRQ-I component was comparable to the original SGRQ (Symptoms 0.62; Activities 0.80; Impacts 0.85).\ud \ud Conclusions The SGRQ-I contains items from the original SGRQ that are the most reliable for measuring health-related quality of life in patients with IPF.

This commentary highlights the present dilemmas surrounding the classification of a patient with interstitial pneumonia who has clinical features suggesting an associated connective tissue disease but the features fall short of a clear diagnosis of connective tissue disease-associated interstitial lung disease under the current rheumatologic classification systems. This commentary illustrates what we perceive to be the limitations in the present approach to the classification of this group of patients and discusses problems with redefining the diagnosis of undifferentiated connective tissue disease to encompass patients with interstitial pneumonia. Finally, we advocate not only for a multidisciplinary approach to evaluation, but also disease classification and offer a proposal to define them as a distinct phenotype—lung-dominant CTD—for which prognostic, therapeutic, and pathobiologic implications can be tested in future, hopefully multiinstitutional, studies.

Patients with idiopathic pulmonary fibrosis (IPF) face a poor prognosis and endure intrusive symptoms that impair quality of life. Many patients with IPF will require supplemental oxygen (O2) at some point in the course of their illness, and although it can improve blood oxygen and symptoms, O2 creates physical and emotional challenges for patients and their loved ones. Four events in the course of IPF—the first occurs at the time of diagnosis and the other three are related to O2—herald periods of transition for patients and their caregivers and mark touchpoints when they need extra care and support from practitioners.