Interstitial Lung Disease Center Research Articles

Riociguat for idiopathic interstitial pneumonia-associated pulmonary hypertension (RISE-IIP): a randomised, placebo-controlled phase 2b study

Idiopathic interstitial pneumonias are often complicated by pulmonary hypertension, increasing morbidity and mortality. There are no approved treatments for pulmonary hypertension associated with idiopathic interstitial pneumonia (PH-IIP). We aimed to evaluate the efficacy and safety of riociguat in patients with PH-IIP. RISE-IIP was a double-blind, randomised, placebo-controlled study done at 65 pulmonary hypertension and interstitial lung disease centres in 19 countries to evaluate the efficacy and safety of riociguat in patients with PH-IIP. Eligible patients were adults (aged 18-80 years) diagnosed with idiopathic interstitial pneumonia (as per American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines), forced vital capacity (FVC) of at least 45%, 6MWD of 150-450 m, WHO functional classes II-IV, precapillary pulmonary hypertension confirmed by right heart catheterisation, systolic blood pressure of at least 95 mm Hg, and no signs or symptoms of hypotension. Patients were randomly allocated (1:1) using an interactive voice and web response system to riociguat (0·5-2·5 mg three times daily) or placebo for 26 weeks (main study), after which they could enter an open-label extension in which all patients received riociguat. The primary endpoint was change in 6-min walking distance (6MWD) in the intention-to-treat population. Prespecified safety variables included adverse events and serious adverse events, laboratory parameters, and adverse events of special interest (haemoptysis and symptomatic hypotension), assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02138825. Between June 4, 2014, and May 5, 2016, we enrolled 229 participants. After the exclusion of 82 participants, 147 were randomly allocated to treatment (73 to riociguat, 74 to placebo). The study was terminated early (median treatment duration 157 days [range 6-203]) at the request of the data monitoring committee owing to increased serious adverse events (main study: 27 [37%] of 73 participants in the riociguat group vs 17 [23%] of 74 in the placebo group) and mortality in patients receiving riociguat, and the absence of efficacy signals in the riociguat group. 11 patients died in the main study (eight in the riociguat group, three in the placebo group), and nine died in the extension phase (one in the riociguat group, eight in the former placebo group; all received riociguat). In the main study, the most common adverse events were peripheral oedema (16 [22%] of 73 in the riociguat group vs seven [9%] of 74 in the placebo group) and diarrhoea (11 [15%] vs seven [9%]). The most common serious adverse events were worsening of interstitial lung disease (main study: six [8%] of 73 in the riociguat group vs five [7%] of 74 in the placebo group) and pneumonia (four [5%] vs one [1%]). Riociguat did not improve 6MWD versus placebo at 26 weeks (least-squares mean difference 21 m; 95% CI -9 to 52). In patients with PH-IIP, riociguat was associated with increased serious adverse events and mortality, and an unfavourable risk-benefit profile. Riociguat should not be used in patients with PH-IIP. Bayer AG and Merck & Co.

Risk factors for diagnostic delay in idiopathic pulmonary fibrosis

BackgroundSurveys and retrospective studies of patients with idiopathic pulmonary fibrosis (IPF) have shown a significant diagnostic delay. However, the causes and risk factors for this delay are not known.MethodsDates at six time points before the IPF diagnosis (onset of symptoms, first contact to a general practitioner, first hospital contact, referral to an interstitial lung disease (ILD) centre, first visit at an ILD centre, and final diagnosis) were recorded in a multicentre cohort of 204 incident IPF patients. Based on these dates, the delay was divided into specific patient-related and healthcare-related delays. Demographic and clinical data were used to determine risk factors for a prolonged delay, using multivariate negative binomial regression analysis.ResultsThe median diagnostic delay was 2.1 years (IQR: 0.9–5.0), mainly attributable to the patients, general practitioners and community hospitals. Male sex was a risk factor for patient delay (IRR: 3.84, 95% CI: 1.17–11.36, p = 0.006) and old age was a risk factor for healthcare delay (IRR: 1.03, 95% CI: 1.01–1.06, p = 0.004). The total delay was prolonged in previous users of inhalation therapy (IRR: 1.99, 95% CI: 1.40–2.88, p < 0.0001) but not in patients with airway obstruction. Misdiagnosis of respiratory symptoms was reported by 41% of all patients.ConclusionDespite increased awareness of IPF, the diagnostic delay is still 2.1 years. Male sex, older age and treatment attempts for alternative diagnoses are risk factors for a delayed diagnosis of IPF. Efforts to reduce the diagnostic delay should focus on these risk factors.Trial registrationThis study was registered at http://clinicaltrials.gov (NCT02772549) on May 10, 2016.

Eligibility for anti-fibrotic treatment in idiopathic pulmonary fibrosis depends on the predictive equation used for pulmonary function testing.

Publicly funded therapy for idiopathic pulmonary fibrosis (IPF) relies on percentage predicted values from pulmonary function testing, for example Australian patients must have a forced vital capacity ≥50% (%FVC), transfer factor of the lung for carbon monoxide ≥ 30% (%TLco) and forced expiratory volume in 1 s (FEV1 )/FVC ratio > 0.7. Despite defined cut-off values, no jurisdiction prescribes a reference equation for use; multiple equations exist. We hypothesized that access to subsidized treatment varies depending on the chosen equation. The %FVC and %TLco from different commonly used reference equations across general respiratory patients, and IPF-specific patients, were compared. FVC and TLco measurements from a large general respiratory laboratory and the Australian Idiopathic Pulmonary Fibrosis Registry (AIPFR) database were analysed using multiple equations. Differences between %FVC and %TLco for each equation were calculated, with particular interest in classification of patients (%) at the threshold for subsidized treatment. A total of 20 378 general respiratory database results were analysed. The %FVC ≥ 50% increased from 86% with the Roca equation to 96% with Quanjer (European Coal and Steal Community, ECSC) and %TLco≥30% increased from 91% with Paoletti to 98% with Thompson. However, overall increase in eligibility for subsidized treatment was modest, varying from 48.2% to 49.2%. A total of 545 AIPFR database results were analysed. The %FVC ≥ 50% increased from 73% with Roca to 94% with Quanjer (ECSC) and %TLco≥30% increased from 87% with Paoletti to 96% with Miller. Overall eligibility for subsidized treatment in the AIPFR group varied from 73.6% to 82.8% between surveyed interstitial lung disease (ILD) centres based entirely on the equation used. Substantial variability exists between reference equations, impacting access to subsidized treatment. Treating clinicians should be aware of this when assessing patients around public funding thresholds.

Characteristics of lung cancer among patients with idiopathic pulmonary fibrosis and interstitial lung disease \u2013 analysis of institutional and population data

BackgroundLung Cancer is occasionally observed in patients with Idiopathic Pulmonary Fibrosis (IPF). We sought to describe the epidemiologic and clinical characteristics of lung cancer for patients with IPF and other interstitial lung disease (ILD) using institutional and statewide data registries.MethodsWe conducted a retrospective analysis of IPF and non-IPF ILD patients from the ILD center registry, to compare with lung cancer registries at the University of Pittsburgh as well as with population data of lung cancer obtained from Pennsylvania Department of Health between 2000 and 2015.ResultsAmong 1108 IPF patients, 31 patients were identified with IPF and lung cancer. The age-adjusted standard incidence ratio of lung cancer was 3.34 (with IPF) and 2.3 (with non-IPF ILD) (between-group Hazard ratio = 1.4, p = 0.3). Lung cancer worsened the mortality of IPF (p < 0.001). Lung cancer with IPF had higher mortality compared to lung cancer in non-IPF ILD (Hazard ratio = 6.2, p = 0.001). Lung cancer among IPF was characterized by a predilection for lower lobes (63% vs. 26% in non-IPF lung cancer, p < 0.001) and by squamous cell histology (41% vs. 29%, p = 0.07). Increased incidence of lung cancer was observed among single lung transplant (SLT) recipients for IPF (13 out of 97, 13.4%), with increased mortality compared to SLT for IPF without lung cancer (p = 0.028) during observational period.ConclusionsLung cancer is approximately 3.34 times more frequently diagnosed in IPF patients compared to general population, and associated with worse prognosis compared with IPF without lung cancer, with squamous cell carcinoma and lower lobe predilection. The causality between non-smoking IPF patients and lung cancer is to be determined.

PHYSICIAN CHARACTERISTICS AND TREATMENT STRATEGIES BY PIRFENIDONE DISCONTINUATION RATES IN IDIOPATHIC PULMONARY FIBROSIS: RESULTS FROM AN ONLINE, SELF-ADMINISTERED SURVEY

SESSION TITLE: Diffuse Lung Disease SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 pm - 02:00 pm PURPOSE: Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis (IPF), reduces lung function decline and improves progression-free survival. Although pirfenidone is generally well tolerated, a subset of patients discontinue therapy due to gastrointestinal- and fatigue-related adverse events (AEs). Physician characteristics and treatment strategies stratified by physician-reported patient discontinuation rates due to AEs are described in a varied sample of US pulmonologists. METHODS: An online, self-administered survey was fielded to pulmonologists between April 10 and May 17, 2017. Pulmonologists were included if they spend >20% of their time in direct patient care and had ≥5 patients with IPF receiving antifibrotic therapy. Physicians were stratified by their self-reported proportion of patients discontinuing pirfenidone (≤20% vs. >20%) after answering questions about initiating pirfenidone treatment and management of AEs. RESULTS: A total of 167 pulmonologists responded; 110 (65.9%) and 57 (34.1%) reported ≤20% and >20% of patients discontinuing pirfenidone due to AEs, respectively. In the ≤20% and >20% groups, 41.8% and 36.8%, respectively, practice in an interstitial lung disease center; in both groups, most spend >80% of their time in direct patient care and have 11 to 20 years of experience. More physicians in the ≤20% group practice at an academic medical center vs. the >20% group (63.6% vs. 45.6%, respectively). The mean (SD) number of patients with IPF in each practice was 70.3 (122.7) in the ≤20% group and 60.6 (80.3) in the >20% group. Most physicians in both groups specify when to take pirfenidone relative to a meal (e.g., before, during or after), with the majority counseling during the meal. However, a lower proportion in the ≤20% group recommend during a meal vs. those in the >20% group (56.7% vs. 71.9%, respectively), whereas a higher proportion in the ≤20% group recommend after a meal (28.3% vs. 18.8%, respectively). Physicians in the ≤20% group were less likely to suggest additional therapy to manage AEs, including anti-nausea and anti-diarrheal drugs. Physicians in the ≤20% group were more likely to report strategies to prevent fatigue as being effective than those in the >20% group (33.3% vs. 19.4%, respectively). CONCLUSIONS: Physicians who reported a lower rate of tolerability-related discontinuations (≤20%) had more patients with IPF in their practice. These physicians are more likely to recommend taking pirfenidone after a meal, use fewer additional therapies to manage AEs and reported more-effective strategies to prevent fatigue in their patients vs. physicians with a higher rate of discontinuations (>20%). CLINICAL IMPLICATIONS: Treatment persistence with pirfenidone can be maintained by effective dose titration and AE management strategies. DISCLOSURES: Consultant relationship with Genentech, Inc. Please note: $1001 - $5000 Added 02/21/2018 by Tmirah Haselkorn, source=Web Response, value=Consulting fee No relevant relationships by Peter LaCamera, source=Web Response Employee relationship with Genentech Please note: >$100000 Added 02/23/2018 by Susan Limb, source=Web Response, value=Salary Employee relationship with Genentech, Inc. Please note: >$100000 Added 02/22/2018 by Elizabeth Morgenthien, source=Web Response, value=Salary Stockholder relationship with Roche Please note: $5001 - $20000 Added 02/22/2018 by Elizabeth Morgenthien, source=Web Response, value=Stock Stockholder relationship with Bristol Myers Squibb Please note: $20001 - $100000 Added 02/22/2018 by Elizabeth Morgenthien, source=Web Response, value=Stock Stockholder relationship with Zimmer Please note: $20001 - $100000 Added 02/22/2018 by Elizabeth Morgenthien, source=Web Response, value=Stock Employee Removed 02/22/2018 by John Stauffer, source=Web Response Employee relationship with Genentech, Inc. Please note: $20001 - $100000 Added 02/22/2018 by John Stauffer, source=Web Response, value=Stock holder Speaker/Speaker's Bureau relationship with Genentech, Inc. Please note: $5001 - $20000 Added 02/27/2018 by Mark Wencel, source=Web Response, value=Consulting fee Employee relationship with Genentech, Inc. Please note: >$100000 Added 02/22/2018 by Ming Yang, source=Web Response, value=Salary

Survey of Specialist Pulmonary Medicine Health Care Structures for Patients with Interstitial Lung Disease in Nordrhein-Westfalen, Germany - A Pilot Project of the Western German Respiratory Society (WdGP)

Survey of specialist pulmonary medicine health care structures for patients with interstitial lung disease (ILD) in Nordrhein-Westfalen, Germany. The Western German Respiratory Society initiated a voluntary registration of ILD expert centers. Structural quality and processes were evaluated by questionnaire. 49 centers were registered, 46 allowed analysis of their center data (15 pulmonology specialist practices, 34 hospital pulmonology departments). Specialist practices saw a median of 360 ILD patients per year (26 % first diagnosis), hospital departments a median of 105 ILD patients per year (63 % first diagnosis). 10 centers diagnose more than 100 new ILD cases per year. Specialist practices report median 50 bronchoscopies per year, hospital departments median 1396. 78 % of the centers participate in a multidisciplinary ILD case conference. Several ILD expert centers were identified in Nordrhein-Westfalen. Outpatient care mainly involves the monitoring of ILD patients, inpatient services focus on complex initial diagnostics or cases with unusual disease behaviour. ILD centers meeting regional health care needs should be supported in their development.

Early clinical experiences with nintedanib in three UK tertiary interstitial lung disease centres

BackgroundNintedanib has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis (IPF). It was approved by the National Institute for Health and Care Excellence (NICE) in January 2016 for IPF patients with a forced vital capacity (FVC) of 50–80% in the United Kingdom (UK).AimTo report real world data about our early clinical experience using nintedanib in 187 patients with a multi-disciplinary (MDT) diagnosis of IPF in a manufacturer funded patient in need scheme (three UK centres) prior to NICE approval.MethodsAll patients with a MDT diagnosis of IPF from December 2014 to January 2016 commenced on nintedanib were included. Demographic details, adverse events (AEs) and where available lung function results were retrospectively collected from clinical letters.Results187 patients (76% males) with a median age of 72 years (49–89) were treated with nintedanib. The average pre-treatment FVC was 81.1 ± 19.8% and diffusion capacity of the lungs for carbon monoxide was 43.9 ± 15% (n = 82). Fifty percent of patients started nintedanib because they were ineligible for pirfenidone due to an FVC > 80%. The median treatment course was 8 ± 4 months. The majority of patients experienced 1–3 AEs with nintedanib (52%, n = 97). The most frequent AEs were diarrhoea (50%), nausea (36%), reduced appetite (24%), tiredness (20%) and gastro-oesophageal reflux (18%). The majority of AEs resulted in no change in treatment (64%, n = 461). 21% (n = 150) of AEs resulted in a dose reduction and 13% (n = 94) necessitated discontinuation of treatment. 1 in 5 patients discontinued treatment either temporarily or on a permanent basis during the monitoring period. In a select cohort of patients, a statistically significant greater proportion of patients remained stable or improved and a lower proportion declined, as depicted by FVC changes of > 5% after nintedanib commencement (P < 0.05 using Chi squared test).ConclusionsNintedanib is well tolerated and has an acceptable safety profile. Only 8% of those reporting diarrhoea discontinued treatment either on a temporary or permanent basis. There were no signals with respect to increased cardiovascular morbidity or major bleeding risk. This is in keeping with the INPULSIS clinical trial findings but in a real world cohort.

Autoimmune Hypothyroidism As a Predictor of Mortality in Chronic Hypersensitivity Pneumonitis

Chronic hypersensitivity pneumonitis (CHP) is a fibrotic parenchymal lung disease that occurs when inhalation of environmental antigens leads to immune dysregulation. Autoimmune features have recently been identified as potentially important among patients with CHP. However, the relationship between hypothyroidism (HT) and CHP is unknown. In this study, we investigate the prevalence and impact of HT among patients with CHP. We conducted a retrospective, case-control analysis. We identified 121 patients at the University of Chicago Interstitial Lung Disease Center with a multidisciplinary diagnosis of CHP. These patients were matched 3:1 according to age, sex, and race to 363 control subjects with asthma from 2006 to 2015. We analyzed demographics, clinical characteristics, and survival between both groups and assessed the relationship of HT with CHP. Survival analysis was performed using Cox proportional hazards modeling. Patients with CHP had higher prevalence of HT (25.6%, n = 31) compared to controls (10.7%, n = 39; OR, 2.86; 95% CI, 1.62-4.99; P < 0.0001). Compared to CHP alone, patients with CHP/HT were more likely to be female (80.6 vs 51.1%, P = 0.004), have increased incidence of autoimmune disease (19.4 vs 3.3%, P = 0.009), antinuclear antibody seropositivity (80.6 vs 57.0%, P = 0.019), and higher TSH levels (4.0 vs 1.9 mIU/L, P < 0.0001). HT was a significant independent predictor of mortality among CHP patients with seropositive ANA (HR, 3.39; 95% CI, 1.31-8.80; P = 0.012). HT is common in patients with CHP and may carry prognostic significance in patients with features of autoimmunity. Further research exploring common pathogenic pathways between autoimmune HT and CHP may illuminate the association of HT with survival.

Comprehensive and Individualized Patient Care in Idiopathic Pulmonary Fibrosis: Refining Approaches to Diagnosis, Prognosis, and Treatment

As seen in this CME online activity (available at http://courses.elseviercme.com/chest16/647e), idiopathic pulmonary fibrosis (IPF) is a specific form of chronic progressive fibrotic lung disease of unknown cause. It is the most common form of idiopathic interstitial pneumonia in adults. Its prevalence among US Medicare beneficiaries has more than doubled in the past 14 years. With the approval of two agents that reduce functional decline and disease progression, and the 2015 update of the American Thoracic Society guidelines on the treatment of IPF, the options for appropriate clinical management of the disease have become well defined. Early diagnosis and early initiation of treatment are of critical importance for long-term clinical outcomes. The diagnostic process, which may require a multidisciplinary team of experts, is centered on excluding systemic diseases and exposures and identifying a pattern of usual interstitial pneumonia on high-resolution CT or surgical lung biopsy results. Familiarity with the 2015 American Thoracic Society guidelines is critical with respect to both the treatments that the guidelines recommend and those that they advise against. Standard immunosuppressive therapy is no longer indicated, whereas pirfenidone, nintedanib, and antacid therapy are all conditionally recommended for use. Individualizing treatment is important in light of potential improved adherence to both drug therapy and health behaviors. An early referral to an interstitial lung disease center offers the advantages of comprehensive diagnostic and disease-management expertise, potential enrollment in a clinical trial, and evaluation for transplantation.

Erectile dysfunction is a common problem in interstitial lung diseases.

Introduction: Erectile dysfunction (ED) is related to chronic diseases, including COPD. The pathogenesis may involve chronic hypoxia, which is common in interstitial lung disease (ILD). We aimed to study the relationship between ILD and ED. Method: Male patients with ILD detected by high-resolution computed tomography (HR-CT) and/or histopathological findings in a lung biopsy were prospectively enrolled at two European ILD centers. Participants were asked to fill in the International Index of Erectile Function questionnaire (Danish or Dutch version). Information on type of ILD, lung function tests, 6-minute walking test (6MWT), co-morbidities, medication and smoking history was obtained from patient records.Results: Of 82 enrolled patients, 54 patients (65.9%) returned the questionnaire. Mean age was 66.8 years (SD: 9.03). Twenty-six patients (48.1%) had IPF. Overall, 38 (70.4%) had some degree of ED, thirty (56.6%) had moderate to severe ED, and 23 (43.4%) had severe ED. Low diffusion capacity and high body mass index showed a trend of increasing risk of moderate to severe ED. The risk increased with age (OR per 5-year increase=2.63 (1.25; 5.53)) and decreased with 6MWT distance (OR per 50 m increase=0.60 (0.41; 0.89). Only two patients (6.7%) received specific treatment with phosphodiesterase-5 inhibitors. Conclusion: Severe ED is a common problem in men with ILD, and is associated with poor walking distance and high age. Treatment coverage is low, and physicians should address this problem as a part of the routine care. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 356-364).

The use of pretest probability increases the value of high-resolution CT in diagnosing usual interstitial pneumonia.

Recent studies have suggested that non-definitive patterns on high-resolution CT (HRCT) scan provide sufficient diagnostic specificity to forgo surgical lung biopsy in the diagnosis of idiopathic pulmonary fibrosis (IPF). The objective of this study was to determine test characteristics of non-definitive HRCT patterns for identifying histopathological usual interstitial pneumonia (UIP). Patients with biopsy-proven interstitial lung disease (ILD) and non-definitive HRCT scans were identified from two academic ILD centres. Test characteristics for HRCT patterns as predictors of UIP on surgical lung biopsy were derived and validated in independent cohorts. In the derivation cohort, 64/385 (17%) had possible UIP pattern on HRCT; 321/385 (83%) had inconsistent with UIP pattern. 113/385 (29%) patients had histopathological UIP pattern in the derivation cohort. Possible UIP pattern had a specificity of 91.2% (95% CI 87.2% to 94.3%) and a positive predictive value (PPV) of 62.5% (95% CI 49.5% to 74.3%) for UIP pattern on surgical lung biopsy. The addition of age, sex and total traction bronchiectasis score improved the PPV. Inconsistent with UIP pattern demonstrated poor PPV (22.7%, 95% CI 18.3% to 27.7%). HRCT pattern specificity was nearly identical in the validation cohort (92.7%, 95% CI 82.4% to 98.0%). The substantially higher prevalence of UIP pattern in the validation cohort improved the PPV of HRCT patterns. A possible UIP pattern on HRCT has high specificity for UIP on surgical lung biopsy, but PPV is highly dependent on underlying prevalence. Adding clinical and radiographic features to possible UIP pattern on HRCT may provide sufficient probability of histopathological UIP across prevalence ranges to change clinical decision-making.

A comparison of published multidimensional indices to predict outcome in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) has an unpredictable course and prognostic factors are incompletely understood. We aimed to identify prognostic factors, including multidimensional indices from a significant IPF cohort at the Bristol Interstitial Lung Disease Centre in the UK.Patients diagnosed with IPF between 2007 and 2014 were identified. Longitudinal pulmonary physiology and exercise testing results were collated, with all-cause mortality used as the primary outcome. Factors influencing overall, 12- and 24-month survival were identified using Cox proportional hazards modelling and receiver operating characteristic curve analysis.We found in this real-world cohort of 167 patients, diffusing capacity for carbon monoxide (DLCO) and initiation of long-term oxygen were independent markers of poor prognosis. Exercise testing results predicted 12-month mortality as well as DLCO, but did not perform as well for overall survival. The Composite Physiological Index was the best performing multidimensional index, but did not outperform DLCO. Our data confirmed that patients who experienced a fall in forced vital capacity (FVC) >10% had significantly worse survival after that point (p=0.024).Our data from longitudinal follow-up in IPF show that DLCO is the best individual prognostic marker, outperforming FVC. Exercise testing is important in predicting early poor outcome. Regular and complete review should be conducted to ensure appropriate care is delivered in a timely fashion.

Use of Mycophenolate Mofetil or Azathioprine for the Management of Chronic Hypersensitivity Pneumonitis

The treatment of chronic hypersensitivity pneumonitis (cHP) often includes systemic oral corticosteroids, but the optimal pharmacologic management remains unclear. The morbidity associated with prednisone has motivated the search for alternative therapies. We aimed to determine the effect of treatment with mycophenolate mofetil (MMF) or azathioprine (AZA) on lung function in patients with cHP. Patients with cHP treated with either MMF or AZA were retrospectively identified from four interstitial lung disease centers. Change in lung function before and after treatment initiation was analyzed using linear mixed-effects modeling (LMM), adjusting for age, sex, smoking history, and prednisone use. Seventy patients were included: 51 were treated with MMF and 19 with AZA. Median follow-up after treatment initiation was 11months. Prior to treatment initiation, FVC and diffusion capacity of the lung for carbon monoxide (Dlco) %predicted were declining at a mean rate of 0.12%(P< .001) and 0.10%(P< .001) per month, respectively. Treatment with either MMF or AZA was not associated with improved FVC (0.5%at 1 year; P= .46) but was associated with a statistically significant improvement in Dlco of 4.2%(P< .001) after 1 year of treatment. Results were similar in the subgroup of patients treated with MMF for 1 year; the FVC increased nonsignificantly by 1.3%(P= .103) and Dlco increased by 3.9%(P< .001). Treatment with MMF or AZA is associated with improvements in Dlco in patients with cHP. Prospective randomized trials are needed to validate their effectiveness for cHP.

Evaluating the interstitial lung disease multidisciplinary meeting: a survey of expert centres.

BackgroundMultidisciplinary meetings (MDM) are the current “gold standard” in interstitial lung disease (ILD) diagnosis and comprise inter-disciplinary discussion of multiple forms of information to provide diagnostic and management outputs. Although bias could be potentially inserted at any step in the discussion process, to date there has been no consensus regarding the appropriate constitution and governance of MDM. We sought to determine the features of ILD MDMs based within ILD centres of excellence around the world.MethodsAn internet based questionnaire was sent to twelve expert centres in Europe, North America, and Australia seeking information regarding the structure and governance of their MDM. Data was analysed for consistent themes and points of contrast.ResultsResponses were received from 10 out of 12 centres. Similarities were demonstrated with regards to contributing attendees, meeting frequency and case numbers reviewed. Significant heterogeneity in attendee speciality group type, quantity and method of data presentation, approach to diagnosis formulation and documentation, and information provision was apparent.ConclusionsThe constitution of ILD MDMs differs considerably between expert centres. Such differences may result in discordant outcomes, and emphasise the need for further evidence regarding the appropriate constitution and governance of ILD MDMs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-016-0179-3) contains supplementary material, which is available to authorized users.

Thyroid Disease Is Prevalent and Predicts Survival in Patients With Idiopathic Pulmonary Fibrosis

A significant minority of patients with idiopathic pulmonary fibrosis (IPF) display features of autoimmunity without meeting the criteria for overt connective tissue disease. A link between IPF and other immune-mediated processes, such as hypothyroidism (HT), has not been reported. In this investigation, we aimed to determine whether HT is associated with IPF and if outcomes differ between patients with IPF with and without HT. A retrospective case-control analysis was conducted. Of 311 patients referred to the University of Chicago Interstitial Lung Disease Center with an initial diagnosis of IPF, 196 met the inclusion criteria and were included in the final analysis. Each case was matched 1:1 by age, sex, and race to a control subject with COPD. HT was identified in 16.8% of cases and 7.1% of control subjects (OR, 2.7; 95% CI, 1.31-5.54; P = .01). Among patients with IPF, HT was associated with reduced survival time (P < .001) and was found to be an independent predictor of mortality in multivariable Cox regression analysis (hazard ratio, 2.12; 95% CI, 1.31-3.43; P = .002). A secondary analysis of two IPF clinical trial datasets supports these findings. HT is common among patients with IPF, with a higher prevalence than in those with COPD and the general population. The presence of HT also predicts mortality in IPF, a finding that may improve future prognostication models. More research is needed to determine the biologic link between IPF and HT and how the presence of thyroid disease may influence disease progression.

The palliative care needs for fibrotic interstitial lung disease: A qualitative study of patients, informal caregivers and health professionals

Background: While there have been some studies looking at the impact on quality of life of patients with idiopathic pulmonary fibrosis, to date no qualitative research looking at the specialist palliative needs of these patients has been conducted. Aim: This study aims to explore the specialist palliative care needs of people living with end-stage progressive idiopathic fibrotic interstitial lung disease. Design and settings/participants: In total, 18 qualitative semi-structured in-depth interviews were conducted with patients, their informal caregivers and health professionals across two specialist interstitial lung disease centres in London and in the community. Results: Many participants reported uncontrolled symptoms of shortness of breath, cough and insomnia, which profoundly impacted every part of patients’ and informal caregivers’ lives. Psychologically, patients were frustrated and angry at the way in which their illness severely limited their ability to engage in activities of daily living and compromised their independence. Furthermore, both patients and informal caregivers also reported that the disease seriously affected family relationships where strain was pronounced. There was varied knowledge and confidence among health professionals in managing symptoms, and psychosocial needs were often underestimated. Conclusion: This study is the first of its kind to examine in depth the impact of symptoms and psychosocial needs revealing the profound effect on every aspect of progressive idiopathic fibrotic interstitial lung disease patients’ and informal caregivers’ lives. Education and guidance of appropriate palliative care interventions to improve symptom control are needed. A case conference intervention with individualised care plans may help in addressing the substantial symptom control and psychosocial needs of these patients and informal caregivers.

Effect of Smoking and Gender on Pulmonary Function and Clinical Features in Sarcoidosis

The effect of cigarette smoking on the clinical manifestations and progression of sarcoidosis is not well characterized. We sought to determine the effects of smoking in sarcoidosis patients and to evaluate for gender-specific differences. We examined the effects of cigarette smoking in 518 patients seen at the Sarcoidosis and Interstitial Lung Disease Center at Wayne State University using radiographic pattern, pulmonary function testing, and clinical features of the disease. We performed a separate analysis to evaluate for gender-specific differences based on smoking history. We found that smokers had significantly lower FEV(1) and FEV(1)/FVC values. Total lung capacity was not significantly different between smokers and nonsmokers, but diffusion capacity for carbon monoxide (DL(CO)) was significantly reduced in smokers. Gender-based statistical analysis showed a marked decrease in DL(CO) values among female smokers. Smokers were also found to have a higher incidence of extrapulmonary involvement as multivariate regression analysis demonstrated that both smoking and female gender are significantly associated with the development of extrapulmonary manifestations. Our data indicate that both cigarette smoking and gender are important in shaping the clinical manifestations of sarcoidosis. The nature of the gender difference requires further study and may be related to differences in inflammatory response.

Long-term Course and Prognosis of Idiopathic Pulmonary Fibrosis in the New Millennium

The American Thoracic Society and European Respiratory Society guidelines for the diagnosis and treatment of idiopathic pulmonary fibrosis (IPF) have been published recently. However, the influence, practical application, and utility of the prior consensus statement for IPF have never been evaluated. Demographics, diagnostic criteria, pulmonary function data, and disposition of patients with IPF evaluated at an interstitial lung disease center between 2000 and 2009 were analyzed. Enrollment in clinical drug trials, lung transplantation, and mortality also were assessed. A total of 521 patients with IPF were evaluated, with pulmonary function testing available in 446. In the 64% of patients without surgical lung biopsy, the most common major criterion not fulfilled was bronchoscopy. Lung transplantation was performed in 16.1% of patients, whereas 27.4% of prescreened patients were enrolled in a prospective drug study. Patients with mild, moderate, and severe disease categorized by FVC % predicted had median survivals of 55.6, 38.7, and 27.4 months, respectively. The attrition rate of patients who survived beyond 5 years was attenuated in subsequent years. IPF remains a deadly disease with a poor prognosis. Bronchoscopy does not appear to be required for an accurate diagnosis. A minority of patients were accommodated within a clinical trial or with transplantation. Categorization by baseline FVC % predicted effectively discriminates groups with different long-term outcomes. Our analysis supports the view that the value of statements also can be realized in the subsequent demonstration of their impact on patient management, which might enable further refinements in a continuous, iterative rediscovery process.

Vitamin D Deficiency and Reduced Lung Function in Connective Tissue-Associated Interstitial Lung Diseases

Vitamin D is a steroid hormone with pleiotropic effects including immune system modulation, lung tissue remodeling, and bone health. Vitamin D deficiency has been implicated in the development of autoimmune diseases. We sought to evaluate the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease (ILD) and hypothesized that vitamin D deficiency would be associated with an underlying connective tissue disease (CTD) and reduced lung function. Patients in the University of Cincinnati ILD Center database were evaluated for serum 25-hydroxyvitamin D levels as part of a standardized protocol. Regression analysis evaluated associations between 25-hydroxyvitamin D levels and other variables. One hundred eighteen subjects were included (67 with CTD-ILD, 51 with other forms of ILD). The overall prevalence of vitamin D deficiency and insufficiency in the study population was 38% and 59%, respectively. Those with CTD-ILD were more likely to have vitamin D deficiency (52% vs 20%, P < .0001) and insufficiency (79% vs 31%, P < .0001) than other forms of ILD. Diminished FVC was associated with lower 25-hydroxyvitamin D(3) levels (P = .01). The association between vitamin D insufficiency and CTD-ILD persisted (OR, 11.8; P < .0001) after adjustment for potential confounders. Among subjects with CTD-ILD, reduced 25-hydroxyvitamin D(3) levels were strongly associated with reduced lung function (FVC, P = .015; diffusing capacity for carbon monoxide, P = .004). There is a high prevalence of vitamin D deficiency in patients with ILD, particularly those with CTD-ILD, and it is associated with reduced lung function. Vitamin D may have a role in the pathogenesis of CTD-ILD.

Idiopathic Nonspecific Interstitial Pneumonia

The American Thoracic Society/European Respiratory Society International Consensus Classification panel identified the clinical entity idiopathic nonspecific interstitial pneumonia (NSIP) as a provisional diagnosis and recommended further study. We hypothesized that idiopathic NSIP is an autoimmune disease and the lung manifestation of undifferentiated connective tissue disease (UCTD), a recently described, distinct entity. We studied 28 consecutive patients with idiopathic interstitial pneumonia (IIP) enrolled in the University of California, San Francisco Interstitial Lung Disease Center who met prespecified criteria for UCTD, as follows: at least one clinical manifestation of connective tissue disease, serologic evidence of systemic inflammation in the absence of clinical infection, and absence of sufficient American College of Rheumatology criteria for another connective tissue disease. Medical record reviews, evaluation of radiographs, and scoring of lung biopsies were performed. The control group consisted of all other patients (n = 47) with IIP who did not meet the UCTD criteria. The patients with UCTD were more likely to be women, younger, and nonsmokers than the IIP control subjects. Compared with the control group, patients with UCTD-ILD were significantly more likely to have ground-glass opacity on high-resolution computed tomography (HRCT) and NSIP pattern on biopsy, and less likely to have honeycombing on HRCT or usual interstitial pneumonia on biopsy. At our center, the majority of patients classified as idiopathic NSIP (88%) met the criteria for UCTD. Most patients diagnosed with idiopathic NSIP meet the case definition of UCTD. Furthermore, these results show that the clinical entity idiopathic NSIP is different from idiopathic pulmonary fibrosis and appears to be an autoimmune disease.