Theodoros Karampitsakos

Safety and efficacy of nintedanib in idiopathic pulmonary fibrosis: A real-life observational study in Greece

BACKGROUND Nintedanib represents an antifibrotic compound able to slow down disease progression of patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVE To investigate the safety and efficacy of nintedanib in patients with IPF in a real-life setting. METHODS This was a multicentre, retrospective, observational, real-life study for patients with IPF receiving nintedanib between October 2014 and October 2016. RESULTS We identified 94 patients with IPF receiving nintedanib (72 males, mean age±SD: 73.8 ± 7.5, mean%FVC±SD = 68.1 ± 18.3, mean%DLCo±SD = 44.4 ± 14.5). Diarrhea (n = 52, 55.3%) was the most commonly reported adverse event. Twenty patients (21.2%) had to permanently discontinue nintedanib due to severe adverse events. In the 6-months follow-up, median decline in %FVC predicted and %DLCO predicted were 1.36 (95%Cl: 0 to 2.97) and 4.00 (95%Cl: 2.01 to 6.20), respectively, when deaths were censored and excluded from the analysis. At 12 months, mean%FVC±SD and mean%DLCo±SD were 64.5 ± 19.1 and 43.7 ± 15.4, respectively. With regards to mortality, 17 patients (18.1%) died over a study period of 730 days. CONCLUSION Nintedanib demonstrated an acceptable safety and efficacy profile in our real-world observational study. Prospective observational studies in the context of registries that collect well-defined supporting data over time are sorely needed to answer residual questions on drugs performance.

Longitudinal “Real-World” Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece

Background Pirfenidone is an antifibrotic compound able to slow down disease progression in patients with idiopathic pulmonary fibrosis (IPF). Objective To investigate the safety and efficacy of pirfenidone in patients with IPF in a real-life setting. Methods This was a multicenter, retrospective, real-life, observational study for patients with IPF receiving pirfenidone. Results We identified 92 patients with IPF receiving pirfenidone. Eighty patients (70 males and 10 females, mean age ± SD: 68.1 + 7.5, mean %FVC ± SD = 74.9 ± 17.2, mean %DLCO ± SD = 48.1 ± 16.9) were included in the analysis. Skin-related (25%) and gastrointestinal (17.5%) adverse events were the most common and led to drug discontinuation in 22.5% of cases. The majority (87%) of patients experienced side effects during the first 6 months of treatment. At 36 months, changes in %FVC and %DLCO were −9.25 ± 16.34 and −9.26 ± 15.26, respectively. At 6, 12, and 24 months after treatment initiation (n = 80, 60, and 26), 18, 15, and 5 patients (22.5, 25, and 19.2%) experienced significant (>10%) and 11, 3, and 3 patients (13.8, 5, and 11.5%) experienced marginal (5–10%) %FVC improvement; and 13, 6, and 1 patient (16.2, 10, and 3.9%) experienced marginal (−5 to −10%) and 20, 21, and 8 patients (25, 35, and 30.8%) experienced significant decline (<−10%) in %FVCpred. Median survival was 851 days, and 41 patients died during the study period. Conclusion Pirfenidone demonstrated an acceptable safety and therapeutic profile in patients with IPF on a longitudinal basis. Prospective observational registries are urgently needed to provide a real-world view of outcomes of pirfenidone in clinical practice.

Greek Physicians’ Perceptions on Generic Drugs in the Era of Austerity

Purpose. To assess the beliefs and preferences of Greek physicians, regarding generic drugs, in the years of financial crisis. Setting. Multicentered, nationwide survey. Material and Methods. A custom questionnaire based on former similar studies was developed and administered to Greek physicians. The variable “perception on generics” was constructed after an exploratory study and the instrument was validated by conventional and Rasch analysis methods. 22 items formed 5 subscales that constructed the variable in question. Results. 908 physicians successfully participated in the study (response rate: 80%). Mean total scores to the instrument were 60.63 ± 12.12 for men and significantly less (58.24 ± 11.73) for women (p = 0.04). Greek physicians were not persuaded on the potential economic gain (45.79 ± 10.53); moreover they identified that Greek authorities cannot address the increased pharmacovigilance mandates. Physicians working in Athens and those working in surgical units demonstrated significantly worse scores than their colleagues from the rest of Greece and those working in Internal Medicine wards (p = 0.03).  Conclusion. Our results suggest an overall poor acceptance of the national initiative on generic drugs by Greek physicians. This trial is registered with Clinicaltrials.gov identifier: NCT01855802.

Pulmonary hypertension in patients with interstitial lung disease

Interstitial lung diseases (ILDs) comprise a broad and heterogeneous group of more than two hundred diseases with common functional characteristics. Their diagnosis and management require a multidisciplinary approach. This multidisciplinary approach involves the assessment of comorbid conditions including pulmonary hypertension (PH) that exerts a dramatic impact on survival. The current World Health Organization (WHO) classification of PH encompasses many of the interstitial lung diseases into WHO Group 3, while sarcoidosis, Pulmonary Langerhans Cell Histiocytosis and lymphangioleiomyomatosis are placed into WHO Group 5 as diseases with unclear or multifactorial mechanisms. Connective tissue diseases could span any of the 5 WHO groups based on the primary phenotype into which they manifest. Interestingly, several challenging phenotypes present with features that overlap between two or more WHO PH groups. Currently, PH-specific treatment is recommended only for patients classified into WHO Group 1 PH. The lack of specific treatment for other groups, including PH in the setting of ILD, reflects the poor outcomes of these patients. Thus, identification of the optimal strategy for ILD patients with PH remains an amenable need. This review article provides a brief overview of biomarkers indicative of vascular remodeling in interstitial lung disease, summarizes the current state of knowledge regarding patients with PH and ILD and highlights future perspectives that remain to be addressed.

Metabolic Disorders in Chronic Lung Diseases

Chronic lung diseases represent complex diseases with gradually increasing incidence, characterized by significant medical and financial burden for both patients and relatives. Their increasing incidence and complexity render a comprehensive, multidisciplinary, and personalized approach critically important. This approach includes the assessment of comorbid conditions including metabolic dysfunctions. Several lines of evidence show that metabolic comorbidities, including diabetes mellitus, dyslipidemia, osteoporosis, vitamin D deficiency, and thyroid dysfunction have a significant impact on symptoms, quality of life, management, economic burden, and disease mortality. Most recently, novel pathogenetic pathways and potential therapeutic targets have been identified through large-scale studies of metabolites, called metabolomics. This review article aims to summarize the current state of knowledge on the prevalence of metabolic comorbidities in chronic lung diseases, highlight their impact on disease clinical course, delineate mechanistic links, and report future perspectives on the role of metabolites as disease modifiers and therapeutic targets.

The effect of bronchodilation and spirometry on fractional exhaled nitric oxide (FeNO50), bronchial NO flux (JawNO) and alveolar NO concentration (CANO) in children and young adults

ABSTRACT Objective: Fractional exhaled nitric oxide (FeNO), bronchial nitric oxide (JawNO) and alveoar nitric oxide (CANO) are biomarkers of eosinophilic inflammation, usually measured simultaneously with spirometry and bronchodilation. Our aim was to investigate the effect of bronchodilation and spirometry on FeNO, CANO and JawNO in children and young adults with well-controlled asthma and in healthy volunteers. Methods: FeNO was measured in 95 subjects (62 controls, 33 asthmatics). CANO and JawNO were assessed in 41 of the subjects (35 healthy, 6 asthmatics.) Measurements were performed before spirometry (1), right after spirometry (2), 20 min after the first spirometry and bronchodilation (3), right after the post-bronchodilation spirometry (4) and 30 min after the last spirometry (5). Results: The presence of well-controlled asthma was not associated with different pattern of reaction after spirometry and bronchodilation. A statistically significant difference was observed only between FeNO4 and FeNO5, as well as between CANO1 and CANO3 (19.14 ± 1.68 vs 20.62 ± 1.85 ppb, p = 0.001 and 4.42 ± 0.40 vs 3.09±0.32 ppb, p = 0.001, respectively). Conclusions: Spirometry and bronchodilation have an insignificant effect on FeNO and JawNO. Even if a slight change occurs in FeNO and JawNO, this does not modify clinicians decision and therapeutic strategy. CANO values (CANO1) are significantly decreased 20 min after spirometry and bronchodilation.

Corrigendum: Longitudinal “Real-World” Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece

[This corrects the article on p. 213 in vol. 4, PMID: 29238708.].

A Rare Case of Primary Intrapulmonary Neurilemmoma Diagnosed in a 43-Year-Old Asymptomatic Man with a Well-defined Intrapulmonary Mass

Neurilemmoma (NL), also termed schwannoma, presents as a well-circumscribed and encapsulated mass in the human body and is almost always solitary. CT scan of a patient with NL shows a round, ovoid, or lobulated well-demarcated solid mass of soft tissue density. Primary intrathoracic neurogenic tumors location varies. However, the development of such tumors is by far more common in the costovertebral angle of the posterior mediastinum. Here, we report a rare case of a 43-year-old patient, never smoker and previously healthy, who presented with a mass adjacent to the right pulmonary hilum. This was an incidental finding on a chest X-ray after annual checkup at his workplace. The diagnosis was primary intrapulmonary NL. Primary intrapulmonary NL is an extremely rare tumor. However, based on the above, chest CT findings of a well-defined solid mass in an asymptomatic patient should raise the suspicion of NL, irrespective of the tumor localization.

Early Career Members at the ERS Lung Science Conference: cell-matrix interactions in lung disease and regeneration: Early career forum

The 16th ERS Lung Science Conference (LSC) took place on March 8–11, 2018, in Estoril, Portugal, with around 200 delegates from all over the world. This year’s topic was “Cell-matrix interactions in lung disease and regeneration” and involved excellent presentations by leading experts in the field covering everything from exploratory studies on how the matrix functions, matrix remodelling and biomarkers in disease, to more technical knowledge described in the field of lung bioengineering. As in previous years, the Saturday afternoon was reserved for a programme dedicated to early career delegates, which this year focussed on “Maximising your publication output”. In this article, we summarise the Early Career Member highlights of this year’s LSC. .@EarlyCareerERS looks back on #LSC2018 http://ow.ly/6hjS30jB6P9