Julie Morisset

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

BACKGROUND: 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. METHODS: 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. RESULTS: Seventy patients were included: 51 were treated with MMF and 19 with AZA. Median follow‐up after treatment initiation was 11 months. 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). CONCLUSIONS: 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.

Home monitoring improves endpoint efficiency in idiopathic pulmonary fibrosis

The objective of this study was to investigate the reliability, feasibility and analytical impact of home-based measurement of forced vital capacity (FVC) and dyspnoea as clinical endpoints in idiopathic pulmonary fibrosis (IPF). Patients with IPF performed weekly home-based assessment of FVC and dyspnoea using a mobile hand-held spirometer and self-administered dyspnoea questionnaires. Weekly variability in FVC and dyspnoea was estimated, and sample sizes were simulated for a hypothetical 24-week clinical trial using either traditional office-based interval measurement or mobile weekly assessment. In total, 25 patients were enrolled. Mean adherence to weekly assessments over 24 weeks was greater than 90%. Compared with change assessment using baseline and 24-week measurements only, weekly assessment of FVC resulted in enhanced precision and power. For example, a hypothetical 24-week clinical trial with FVC as the primary endpoint would require 951 patients using weekly home spirometry compared with 3840 patients using office spirometry measures at weeks 1 and 24 only. The ability of repeated measures to reduce clinical trial sample size was influenced by the correlation structure of the data. Home monitoring can improve the precision of endpoint assessments, allowing for greater efficiency in clinical trials of therapeutics for IPF. Home monitoring improves endpoint efficiency in idiopathic pulmonary fibrosis #AdvancesinILD @ERSTalk http://ow.ly/F5L930bUypH

Identification of Diagnostic Criteria for Chronic Hypersensitivity Pneumonitis. An International Modified Delphi Survey

Rationale: Current diagnosis of chronic hypersensitivity pneumonitis (cHP) involves considering a combination of clinical, radiological, and pathological information in multidisciplinary team discussions. However, this approach is highly variable with poor agreement between centers. Objectives: We aimed to identify diagnostic criteria for cHP that reach consensus among international experts. Methods: A three‐round modified Delphi survey was conducted between April and August 2017. A total of 45 experts in interstitial lung disease from 14 countries participated in the online survey. Diagnostic items included in round 1 were generated using expert interviews and literature review. During rounds 1 and 2, experts rated the importance of each diagnostic item on a 5‐point Likert scale. The a priori threshold of consensus was 75% or greater of experts rating a diagnostic item as very important or important. In the third round, experts graded the items that met consensus as important and provided their level of diagnostic confidence for a series of clinical scenarios. Measurements and Main Results: Consensus was achieved on 18 of the 40 diagnostic items. Among these, experts gave the highest level of importance to the identification of a causative antigen, time relation between exposure and disease, mosaic attenuation on chest imaging, and poorly formed nonnecrotizing granulomas on pathology. In clinical scenarios, the diagnostic confidence of experts in cHP was heightened by the presence of these diagnostic items. Conclusions: This consensus‐based approach for the diagnosis of cHP represents a first step toward the development of international guidelines for the diagnosis of cHP.

Mortality risk prediction in scleroderma-related interstitial lung disease: the SADL model

BACKGROUND: Interstitial lung disease (ILD) is an important cause of morbidity and mortality in patients with scleroderma (Scl). Risk prediction and prognostication in patients with Scl‐ILD are challenging because of heterogeneity in the disease course. METHODS: We aimed to develop a clinical mortality risk prediction model for Scl‐ILD. Patients with Scl‐ILD were identified from two ongoing longitudinal cohorts: 135 patients at the University of California, San Francisco (derivation cohort) and 90 patients at the Mayo Clinic (validation cohort). Using these two separate cohorts, a mortality risk prediction model was developed and validated by testing every potential candidate Cox model, each including three or four variables of a possible 19 clinical predictors, for time to death. Model discrimination was assessed using the C‐index. RESULTS: Three variables were included in the final risk prediction model (SADL): ever smoking history, age, and diffusing capacity of the lung for carbon monoxide (% predicted). This continuous model had similar performance in the derivation (C‐index, 0.88) and validation (C‐index, 0.84) cohorts. We created a point scoring system using the combined cohort (C‐index, 0.82) and used it to identify a classification with low, moderate, and high mortality risk at 3 years. CONCLUSIONS: The SADL model uses simple, readily accessible clinical variables to predict all‐cause mortality in Scl‐ILD.

A case of difficult-to-treat eosinophilic asthma controlled with clarithromycin

We have shown that measurement of eNO in the normal range has a good specificity for screening out children for EoE, however, eNO is poor at identifying EoE. Testing with eNO may have clinical utility during the evaluation of EoE. When the eNO level was normal, this correctly identified more than 86% of those who did not have EoE. The measurement of eNO does not replace the required diagnostic test of an upper endoscopy with biopsy of the esophagus. Nevertheless, a normal eNO could be helpful in the approach of those EoE-suspicious children that do not have asthma, but elevated measurements were not sensitive for EoE in children. Elevated eNO levels corresponded more with respiratory airway inflammation and not with esophageal inflammation. Limitations to our results are that this was a small pilot study in only children with suspected EoE that were referred to an allergy/ immunology clinic. No children with asthma or those on PPI therapy were studied due to the confounding effect this would have on eNO. Future directions for use of eNO in EoE should be targeted to those with elevated measurements during treatment interventions.

Air Pollution Exposure Is Associated With Lower Lung Function, but Not Changes in Lung Function, in Patients With Idiopathic Pulmonary Fibrosis

BACKGROUND: Air pollution exposure is associated with acute exacerbation, disease progression, and mortality in patients with idiopathic pulmonary fibrosis (IPF). The objective of this study was to describe the impact of air pollution exposures on disease severity, as well as changes in lung function, in patients with IPF. METHODS: Using home spirometers and symptom diaries, 25 patients with IPF prospectively recorded FVC weekly for up to 40 weeks. Residential addresses were geocoded to estimate weekly mean air pollution exposures for ground‐level ozone (O3), nitrogen dioxide (NO2), and particulate matter < 2.5 or 10 &mgr;m in aerodynamic diameter (PM2.5 and PM10, respectively). The dependence of weekly clinical measurements on preceding levels of each pollutant was assessed with the use of linear mixed models, yielding beta‐coefficients with 95% CIs, using varying lag times. RESULTS: Lower mean FVC % predicted was consistently associated with increased mean exposures to PM10 in the 2 to 5 weeks preceding clinical measurements (range, –0.46 to –0.39 [95% CI, –0.73 to –0.13]; P < .005). Lower mean FVC % predicted over the study period was inversely related to mean levels of NO2 (–0.45 [95% CI, –0.85 to –0.05]; P = .03), PM2.5 (–0.45 [95% CI, –0.84 to –0.07]; P = .02), and PM10 (–0.57 [95% CI, –0.92 to –0.21]; P = .003), averaged over the study. Weekly changes in FVC and changes over 40 weeks were independent of pollution exposures. CONCLUSIONS: Higher air pollution exposures were associated with lower lung function, but not changes in lung function, in patients with IPF. Further studies are needed to characterize the mechanisms underlying this relationship.

The Canadian Registry for Pulmonary Fibrosis: Design and Rationale of a National Pulmonary Fibrosis Registry

Background. The relative rarity and diversity of fibrotic interstitial lung disease (ILD) have made it challenging to study these diseases in single-centre cohorts. Here we describe formation of a multicentre Canadian registry that is needed to describe the outcomes of fibrotic ILD and to enable detailed healthcare utilization analyses that will be the cornerstone for future healthcare planning. Methods. The Canadian Registry for Pulmonary Fibrosis (CARE-PF) is a prospective cohort anticipated to consist of at least 2,800 patients with fibrotic ILD. CARE-PF will be used to (1) describe the natural history of fibrotic ILD, specifically determining the incidence and outcomes of acute exacerbations of ILD subtypes and (2) determine the impact of ILD and acute exacerbations of ILD on health services use and healthcare costs in the Canadian population. Consecutive patients with fibrotic ILD will be recruited from five Canadian ILD centres over a period of five years. Patients will be followed up as clinically indicated and will complete standardized questionnaires at each clinic visit. Prespecified outcomes and health services use will be measured based on self-report and linkage to provincial health administrative databases. Conclusion. CARE-PF will be among the largest prospective multicentre ILD registries in the world, providing detailed data on the natural history of fibrotic ILD and the healthcare resources used by these patients. As the largest and most comprehensive cohort of Canadian ILD patients, CARE-PF establishes a network for future clinical research and early phase clinical trials and provides a platform for translational and basic science research.

Rheumatoid Arthritis-Associated Interstitial Lung Disease

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a frequent and clinically important extra-articular manifestation of RA. Although most patients with RA-ILD will experience disease progression over time, RA-ILD encompasses a wide range of disease severity. Early recognition of RA-ILD is essential to ensure adequate patient care. This chapter will review the epidemiology, clinical presentation, evaluation, diagnosis, and natural history of RA-ILD.

Mortality in interstitial lung disease: do race and skin colour matter?

In recent years, research surrounding health disparities has begun to focus more on the complex relationship between race, genetics and disease. Race has come to be recognised as an important factor, not only when discussing disparities and determining policy, but also in the diagnosis, approach and response to treatment. African-Americans with interstitial lung disease exhibit a unique clinical phenotype http://ow.ly/NId830k4c0c

Comprehensive management of fibrotic interstitial lung diseases: A Canadian Thoracic Society position statement

Abstract The comprehensive management of patients with fibrotic interstitial lung disease (ILD) is multi-faceted and may include pharmacological and non-pharmacological therapies. There are no current recommendations and few resources to guide the management of patients with fibrotic ILD in Canada. This position statement provides recommendations for the management of patients with fibrotic ILD based on review of the scientific literature and consensus from a panel of ILD experts. These recommendations relate to important clinically relevant questions, and key messages are provided to guide clinical practice.