Pirfenidone, as compared with placebo, reduced disease progression, as reflected by lung function, exercise tolerance, and progression-free survival, in patients with idiopathic pulmonary fibrosis. Treatment was associated with an acceptable side-effect profile and fewer deaths. (Funded by InterMune; ASCEND ClinicalTrials.gov number, NCT01366209.).

Objective: To describe spirometric reference equations for healthy Brazilian adults who have never smoked and to compare the predicted values with those derived in 1992. Methods: Reference equations for spirometry were derived in 270 men and 373 women living in eight cities in Brazil. Ages ranged from 20 to 85 years in women and from 26 to 86 years in men. Spirometry examinations followed the recommendations of the Brazilian Thoracic Society. Lower limits were derived by the analysis of the fifth percentiles of the residuals. Results: Forced vital capacity (FVC), forced expiratory volume in one second (FEV 1 ), FEV 1 /FVC and FEV 1 /forced expiratory volume in six seconds (FEV 6 ) were best fitted by linear regression. Flows were best fitted using log equations. For both genders, greater height resulted in lower values for FEV 1 /FVC, FEV 1 /FEV 6 and flow/FVC ratios. The reference values for FEV 1 and FVC in the present study were higher than those derived for Brazilian adults in 1992. Conclusion: New predicted values for forced spirometry were obtained in a sample of white Brazilians. The values are greater than those obtained in 1992, probably due to technical factors.

Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression.All patients randomised to pirfenidone 2403 mg·day−1 or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol.A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3–55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0–96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation.Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF.

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BackgroundThe assessment of treatment response in idiopathic pulmonary fibrosis (IPF) is complicated by the variable clinical course. We examined the variability in the rate of disease progression and evaluated the effect of continued treatment with pirfenidone in patients who experienced meaningful progression during treatment.MethodsThe source population included patients enrolled in the ASCEND and CAPACITY trials (N=1247). Pearson's correlation coefficients were used to characterise the relationship between changes in FVC during consecutive 6-month intervals in the placebo population. Outcomes following a ≥10% decline in FVC were evaluated by comparing the proportion of patients in the pirfenidone and placebo groups who experienced a ≥10% decline in FVC or death during the subsequent 6 months.ResultsA weak negative correlation was observed between FVC changes during consecutive intervals in the placebo population (coefficient, −0.146, p<0.001), indicating substantial variability. Thirty-four (5.5%) and 68 (10.9%) patients in the pirfenidone and placebo groups, respectively, experienced a ≥10% decline in FVC by month 6. During the subsequent 6 months, fewer patients in the pirfenidone group compared with placebo experienced a ≥10% decline in FVC or death (5.9% vs 27.9%; relative difference, 78.9%). There was one (2.9%) death in the pirfenidone group and 14 (20.6%) deaths in the placebo group (relative difference, 85.7%).ConclusionsLongitudinal FVC data from patients with IPF showed substantial intrasubject variability, underscoring the inability to reliably assess therapeutic response using serial FVC trends. In patients who progressed during treatment, continued treatment with pirfenidone resulted in a lower risk of subsequent FVC decline or death.Trial registration numbersNCT01366209, NCT00287729, NCT00287716.

A 6-min step test (6MST) may constitute a practical method for routinely assessing effort tolerance and exercise-related oxyhaemoglobin desaturation (ERD) in the primary care of patients with interstitial lung disease.In total, 31 patients (19 males) with idiopathic pulmonary fibrosis (n525) and chronic hypersensitivity pneumonia were submitted, on different days, to two 6MSTs. Physiological responses were compared with those found on maximal and submaximal cycle ergometer tests at the same oxygen uptake (V9O 2 ). Chronic breathlessness was also determined, as measured by the baseline dyspnoea index (BDI).Responses to 6MST were highly reproducible: 1.3¡2.0 steps?min -1 , ¡5 beats?min -1 (cardiac frequency), ¡50 mL?min -1 (V9O 2 ), ¡7 L?min -1 (minute ventilation) and ¡2% (arterial oxygen saturation measured by pulse oximetry (Sp,O 2 )). The number of steps climbed in 6 min was correlated to peak V9O 2 and the BDI. There were significant associations among the tests in relation to presence (change in Sp,O 2 between rest and exercise o4%) and severity (Sp,O 2 ,88%) of ERD. Four patients, however, presented ERD only in response to 6MST. Resting diffusing capacity of the lung for carbon monoxide and alveolar-arterial oxygen tension difference were the independent predictors of the number of steps climbed. A single-stage, self-paced 6-min step test provided reliable and reproducible estimates of exercise capacity and exercise-related oxyhaemoglobin desaturation in interstitial lung disease patients.

BackgroundPirfenidone is an oral antifibrotic agent that has been shown to reduce the decline in lung function in patients with idiopathic pulmonary fibrosis (IPF). We performed an integrated analysis of safety data from five clinical trials evaluating pirfenidone in patients with IPF.MethodsAll patients treated with pirfenidone in the three multinational Phase 3 studies (CAPACITY (studies 004 and 006), ASCEND (study 016)) and two ongoing open-label studies (study 002 and study 012 (RECAP)) were included in the analysis. Safety outcomes were assessed during the period from the first dose until 28 days after the last dose of study drug.ResultsA total of 1299 patients were included in the analysis. The cumulative total exposure to pirfenidone was 3160 person exposure years (PEY). The median duration of exposure was 1.7 years (range 1 week to 9.9 years), and the mean (±SD) daily dose was 2053.8 (±484.9) mg. Gastrointestinal events (nausea (37.6%), diarrhoea (28.1%), dyspepsia (18.4%), vomiting (15.9%)) and rash (25.0%) were the most common adverse events; these were generally mild to moderate in severity and without significant clinical consequence. Elevations in alanine aminotransferase or aspartate aminotransferase greater than three times the upper limit of normal occurred in 40/1299 (3.1%) patients (adjusted incidence, 2.3 per 100 PEY). Elevations were generally transient and reversible with dose modification or discontinuation.ConclusionsA comprehensive analysis of safety outcomes in a large and well-defined cohort of 1299 patients with IPF who were followed prospectively for up to 9.9 years demonstrated that long-term treatment with pirfenidone is safe and generally well tolerated.Trial registration numbersNCT00287716, NCT00287729, NCT00662038, NCT01366209.

Interstitial lung diseases (ILDs) are heterogeneous disorders, involving a large number of conditions, the approach to which continues to pose an enormous challenge for pulmonologists. The 2012 Brazilian Thoracic Association ILD Guidelines were established in order to provide Brazilian pulmonologists with an instrument that can facilitate the management of patients with ILDs, standardizing the criteria used for the diagnosis of different conditions and offering guidance on the best treatment in various situations. The objective of this article was to briefly describe the highlights of those guidelines.Keywords: Lung diseases, interstitial; Guidelines as topic; Brazil. ResumoAs doenças pulmonares intersticiais (DPIs) são afecções heterogêneas, envolvendo um elevado número de condições, cuja abordagem ainda é um grande desafio para o pneumologista. As Diretrizes de DPIs da Sociedade Brasileira de Pneumologia e Tisiologia, publicadas em 2012, foram estabelecidas com o intuito de fornecer aos pneumologistas brasileiros um instrumento que possa facilitar a abordagem dos pacientes com DPIs, padronizando-se os critérios utilizados para a definição diagnóstica das diferentes condições, além de orientar sobre o melhor tratamento nas diferentes situações. Esse artigo teve como objetivo descrever resumidamente os principais destaques dessas diretrizes.Descritores: Doenças pulmonares intersticiais; Guias como assunto; Brasil.