Idiopathic pulmonary fibrosis: From clinical trials to real-life experiences

Randomised controlled clinical trials are fundamental in medicine to develop new effective drugs and new therapeutic regimens and are the strength of evidence-based medicine. These studies allow us to avoid the repetition of misleading experiences that have been reported in the past, where drugs or associations were utilised without compelling evidence and ultimately proven to be ineffective. In recent years, randomised clinical trials have been conducted and concluded for many rare diseases, including idiopathic pulmonary fibrosis. However, clinical trials do not always reflect the real-life scenario. Patients selected for clinical trials present fewer comorbidities, they fall between certain age limits, and the severity of their disease is defined; therefore, they do not always reflect the whole of the population affected by a specific disease. These are the reasons why we also need data that mirror real-life experience. The limitations that these kind of studies present are always several and the studies should be interpreted with caution, although they can fill the important gap between efficacy and effectiveness. In this article, we will review the existing clinical data on real-life treatment of idiopathic pulmonary fibrosis

Pulmonary hypertension in chronic interstitial lung diseases

Pulmonary hypertension (PH) is a common complication of interstitial lung diseases (ILDs), particularly in idiopathic pulmonary fibrosis and ILD associated with connective tissue disease. However, other lung diseases, such as combined pulmonary fibrosis and emphysema syndrome, pulmonary Langerhans cell histiocytosis, and lymphangioleiomyomatosis, may also include PH in their clinical manifestations. In all of these diseases, PH is associated with reduced exercise capacity and poor prognosis. The degree of PH in ILDs is typically mild-to-moderate. However, some of these patients may develop a disproportionate increase in PH that cannot be justified solely by hypoxia and parenchymal injury: this condition has been termed "out-of-proportion" PH. The pathogenesis of PH in these diseases is various, incompletely understood and may be multifactorial. The clinical suspicion (i.e. increased dyspnoea, low diffusion capacity) and echocardiographic assessment are the first steps towards proper diagnosis of PH; however, right heart catheterisation remains the current gold standard for diagnosis of PH. At present, no specific therapies have been approved for the treatment of PH in patients with ILDs. \ua9 ERS 2013

Severe idiopathic pulmonary fibrosis: What can be done?

Idiopathic pulmonary fibrosis (IPF) remains a challenging disease to manage. Two drugs are now available that can slow disease progression in patients with mild-to-moderate IPF. This means that early diagnosis is mandatory, because there are no proven effective therapies for severe IPF. This lack of proven therapies may be at least partially due to the fact that severe IPF patients are usually not enrolled in randomised, prospective, multicentre, international trials. Clinical observation experiences and preliminary results of long-term, open-label extensions of clinical trials suggest that both pirfenidone and nintedanib may also slow or decrease progression in patients with severe IPF. However, data are sparse and obtained from a relatively small number of patients. Lung transplantation should be taken into account early and discussed with patients, when indicated. Rehabilitative strategies are important and effective supportive therapies. The needs of patients with severe IPF are similar to those of patients with an advanced neoplastic disease. Palliative care and psychological support play an important role in the relief of symptoms of anxiety and depression. Accordingly, these therapeutic approaches should start early in IPF patients

New insights in lymphangioleiomyomatosis and pulmonary langerhans cell histiocytosis

Lymphangioleiomyomatosis (LAM) and pulmonary Langerhans cell histiocytosis (PLCH) are rare diseases that lead to progressive cystic destruction of the lungs. Despite their distinctive characteristics, these diseases share several features. Patients affected by LAM or PLCH have similar radiological cystic patterns, a similar age of onset, and the possibility of extrapulmonary involvement. In this review, the recent advances in the understanding of the molecular pathogenesis, as well as the current and most promising biomarkers and therapeutic approaches, are described

Walking distance on 6-MWT is a prognostic factor in idiopathic pulmonary fibrosis

Background and aim of the work: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality rates and a median survival of 2-3 years from time of diagnosis. The prognosis for any individual patient, however, is variable. To elucidate the clinical significance of 6-min walking test (6-MWT) in patients with IPF, we sought to assess the relationship between distance walked and desaturation during this test and pulmonary function tests (PFTs). We also evaluate the prognostic value of 6-MWT in comparison with PFTs at baseline and during follow-up. Methods: The clinical data of 44 patients with IPF were retrospectively analysed. Twenty-nine patients had an additional evaluation after 12 month of follow-up. Results: Distance walked in 6 min was independently related to mortality by multivariate analysis. Patients walking less then 212 m had a significantly lower survival than those walking farther, assessed by Kaplan-Meier survival curves (log-rank test, p < 0.036). During a mean follow-up period of 19.8 months (range 3.2-46.4), 11 patients died of causes related to disease. Changes in meters walked at 12 months evaluation were also predictive of survival (p = 0.05). Conclusions: These results confirm that in IPF distance walked in 6 min is independent associated with mortality

Prevalence of severe asthma according to the drug regulatory agency perspective: An Italian experience

Severe asthma prevalenc

The association between air pollution and the incidence of idiopathic pulmonary fibrosis in Northern Italy

Acute exacerbations and worsening of idiopathic pulmonary fibrosis (IPF) have been associated with exposure to ozone (O3), nitrogen dioxide (NO2) and particulate matter, but chronic exposure to air pollution might also affect the incidence of IPF. We investigated the association between chronic exposure to NO2, O3 and particulate matter with an aerodynamic diameter <10 \u3bcm (PM10) and IPF incidence in Northern Italy between 2005 and 2010. Daily predictions of PM10 concentrations were obtained from spatiotemporal models, and NO2 and O3 hourly concentrations from fixed monitoring stations. We identified areas with homogenous exposure to each pollutant. We built negative binomial models to assess the association between area-specific IPF incidence rate, estimated through administrative databases, and average overall and seasonal PM10, NO2, and 8-hour maximum O3 concentrations. Using unadjusted models, an increment of 10 \u3bcg\ub7m-3 in NO2 concentration was associated with an increase between 7.93% (95% CI 0.36-16.08%) and 8.41% (95% CI -0.23-17.80%) in IPF incidence rate, depending on the season. After adjustment for potential confounders, estimated effects were similar in magnitude, but with larger confidence intervals. Although confirmatory studies are needed, our results trace a potential association between exposure to traffic pollution and the development of IPF

Drift and Equilibrium Selection with Human and Computer Players

The theory of drift (Binmore and Samuelson 1999) concerns equilibrium selection in which second-order disturbances may have first-order effects in the emergence of one equilibrium over the other. We provided experimental evidence with human players supporting the model in Caminati, Innocenti and Ricciuti (2006). In this paper we test it with conditioning by computer players. When computers are removed and humans are matched against each other, the comparative static properties of the model are confirmed