Katerina Dimakou

Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis

In this study the authors investigated whether expiratory flow limitation (FL) is present during tidal breathing in patients with bilateral bronchiectasis (BB) and whether it is related to the severity of chronic dyspnoea (Medical Research Council (MRC) dyspnoea scale), exercise capacity (maximal mechanical power output (WRmax)) and severity of the disease, as assessed by high-resolution computed tomography (HRCT) scoring. Lung function, MRC dyspnoea, HRCT score, WRmax and FL were assessed in 23 stable caucasian patients (six males) aged 56±17 yrs. FL was assessed at rest both in seated and supine positions. To detect FL, the negative expiratory pressure (NEP) technique was used. The degree of FL was rated using a five-point FL score. WRmax was measured using a cyclo-ergometer. According to the NEP technique, five patients were FL during resting breathing when supine but not seated, four were FL both seated and supine, and 14 were NFL both seated and supine. Furthermore, it was shown that: 1) in stable BB patients FL during resting breathing is common, especially in the supine position; 2) the degree of MRC dyspnoea is closely related to the five-point FL score; 3) WRmax (% pred) is more closely correlated with the MRC dyspnoea score than with the five-point FL score; and 4) HRCT score is closely related to forced expiratory volume in one second % pred but not five-point FL score. In conclusion, flow limitation is common at rest in sitting and supine positions in patients with bilateral bronchiectasis. Flow limitation and reduced exercise capacity are both associated with more severe dyspnoea. Finally, high-resolution computed tomography scoring correlates best with forced expiratory volume in one second.

Disseminated tuberculosis complicating anti-TNF-α treatment

An unusually large number of cases of tuberculosis, often of miliary or disseminated form, have been reported in patients receiving infliximab therapy for rheumatoid arthritis or Crohns disease. We describe a patient with rheumatoid arthritis who was treated with infliximab and became systemically ill with Mycobacterium tuberculosis‐disseminated infection. Patients who are candidates for treatment with tumour necrosis factor‐alfa inhibitors should be evaluated for the presence of latent or active M. tuberculosis infection.

Characterization of the “Frequent Exacerbator Phenotype” in Bronchiectasis

Rationale: Exacerbations are key events in the natural history of bronchiectasis, but clinical predictors and outcomes of patients with frequently exacerbating disease are not well described. Objectives: To establish if there is a “frequent exacerbator phenotype” in bronchiectasis and the impact of exacerbations on long‐term clinical outcomes. Methods: We studied patients with bronchiectasis enrolled from 10 clinical centers in Europe and Israel, with up to 5 years of follow‐up. Patients were categorized by baseline exacerbation frequency (zero, one, two, or three or more per year). The repeatability of exacerbation status was assessed, as well as the independent impact of exacerbation history on hospitalizations, quality of life, and mortality. Measurements and Main Results: A total of 2,572 patients were included. Frequent exacerbations were the strongest predictor of future exacerbation frequency, suggesting a consistent phenotype. The incident rate ratios for future exacerbations were 1.73 (95% confidence interval [CI], 1.47‐2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70‐3.66; P < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27‐6.78; P < 0.0001) for patients with three or more exacerbations per year at baseline. Additional independent predictors of future exacerbation frequency were Haemophilus influenzae and Pseudomonas aeruginosa infection, FEV1, radiological severity of disease, and coexisting chronic obstructive pulmonary disease. Patients with frequently exacerbating disease had worse quality of life and were more likely to be hospitalized during follow‐up. Mortality over up to 5 years of follow‐up increased with increasing exacerbation frequency. Conclusions: The frequent exacerbator phenotype in bronchiectasis is consistent over time and shows high disease severity, poor quality of life, and increased mortality during follow‐up.

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.

Investigation of bronchiectasis in severe uncontrolled asthma

The presence of bronchiectasis in patients with asthma varies in different reports, while a clear aetiological relation has not been precisely established.

The role of non-invasive modalities for assessing inflammation in patients with non-cystic fibrosis bronchiectasis

Introduction Bronchiectasis is a heterogeneous entity, taking into account clinical characteristics, inflammatory response, effectiveness of treatment and frequency of exacerbations. In stable state non‐cystic fibrosis (non‐CF) bronchiectasis, little is known about non‐invasive techniques used for evaluating airway inflammation in obstructive airway diseases. Objectives We sought to evaluate the associations between induced sputum and clinical/radiologic characteristics, and the differences between biomarkers expressing Th1 and Th2 response in patients with non‐CF bronchiectasis and to compare our findings with a previously studied population of patients with asthma and COPD. Methods We evaluated prospectively collected data from subjects with bronchiectasis. Comparisons were made between clinical, radiographic and physiologic characteristics, as well as induced sputum markers using appropriate statistical tools. We compared the levels of sputum markers with those of a previously studied cohort of asthma and COPD patients. Results We enrolled 40 subjects (21 men, mean age 63.5 yrs) with bronchiectasis. Fifteen subjects (37.5%) had a neutrophilic phenotype, 7 (17.5%) had an eosinophilic phenotype, 3 (12.5%) had a mixed neutrophilic‐eosinophilic phenotype and 15 (37.5%) had a paucigranulocytic phenotype. Subjects with sputum neutrophilia had more severe bronchiectasis in HRCT and higher levels of IL‐8 in sputum, whereas subjects with eosinophilia had higher levels of FeNO, greater bronchodilator reversibility and higher sputum IL‐13. Sputum IL‐8 levels were higher in subjects exhibiting frequent exacerbations and correlated with neutrophils in sputum (r = 0.799), the extent of bronchiectasis in HRCT (r = 0.765) and post‐bronchodilator FEV1 (r = −0.416). Sputum IL‐13 levels correlated with sputum eosinophils (r = 0.656) and bronchodilator reversibility (r = 0.441). Neutrophilic bronchiectasis exhibited comparable IL‐8 levels to COPD, whereas eosinophilic bronchiectasis showed significantly lower IL‐13 levels compared to asthma. Conclusions Sputum cell counts and IL‐8 and IL‐13 correlate with distinct clinical and functional measurements of disease severity and therefore may have a role for non‐invasively assessing inflammation in non‐cystic fibrosis bronchiectasis. HighlightsInduced sputum is used for assessing airway inflammation in non‐CF bronchiectasis.Interleukin levels in induced sputum may correlate with disease severity.IL‐8 and IL‐13 levels were compared with clinical and laboratory characteristics.IL‐8 was associated with sputum neutrophilia and greater disease severity.IL‐13 was associated with sputum eosinophilia and bronchodilator reversibility.

Telavancin in the treatment of Staphylococcus aureus hospital-acquired and ventilator-associated pneumonia: clinical evidence and experience.

Telavancin (TLV) is a lipoglycopeptide derivative of vancomycin (VAN), which has activity against Gram-positive aerobic bacteria, and is especially effective against methicillin-resistant Staphylococcus aureus (MRSA) and Gram-positive bacteria resistant to VAN. Comparative clinical studies of TLV have demonstrated noninferiority compared with VAN in the treatment of hospital-acquired Gram-positive pneumonia, with high cure rates for TLV-treated patients with monomicrobial S. aureus infection, including isolates with reduced VAN susceptibility. The results based on the patients’ clinical response were supported by supplemental post-hoc analyses of 28-day mortality. In Europe and the USA, TLV is approved as a useful alternative for patients with difficult-to-treat, hospital-acquired MRSA pneumonia when there are very few alternatives. The present article reviews TLV’s pharmacological characteristics and clinical efficacy resulting from clinical trials giving a detailed picture of its properties and position in the management of hospital-acquired pneumonia.

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.