Switching between biologics in severe asthma patients. When the first choice is not proven to be the best.

During the last decades, new treatments targeting disease mechanisms referred as biologics have been introduced in the therapy of asthma and currently, five monoclonal antibodies have been approved. Although these therapeutic agents have been formulated to target specific asthma endotypes, it is often difficult for the treating physician to identify which patient is the best candidate for each one of these specific treatments especially in the clinical scenario of a patient in whom clinical characteristics overlap between different endotypes, allowing the selection of more than one biologic agent. As no head-to-head comparisons between these biologics have been attempted, there is no evidence on the superiority of one biologic agent over the other. Furthermore, a physician's first therapeutic decision, no matter how carefully has been made, may often result in suboptimal clinical response and drug discontinuation, indicating the need for switching to a different biologic. In this short review, we discuss the available evidence regarding the switching between biologics in patients with severe asthma and we propose a simple algorithm on switching possibilities in case that the physicians' initial choice is proven not to be the best.

Asthma and rhinitis in Greek furniture workers.

Objective: The detection of asthma and rhinitis in furniture workers exposed to chemicals in the area of Thessaloniki Greece and the determination of the most useful tests for diagnosing the above occupational diseases.Methods: Eighty-three workers (76 men), 35 exposed to chemicals (CW), 23 to wood dust (WW), and 25 office workers (OW), serving as controls, filled in a specialized European Community Respiratory Health Survey (ECRHS) questionnaire for asthma and were submitted to clinical evaluation, spirometry, bronchodilation test, PEF computer algorithm OASYS-2, FeNO, skin prick tests (SPTs), rhinomanometry and methacholine inhalation challenge. Working conditions and protective measurements were also recorded. According to the results of all conducted tests, each subject was distributed to a subgroup: (a) normal, (b) asthma, (c) rhinitis, (d) asthma and rhinitis. Comparisons were performed among work groups.Results: The presence of asthma and/or rhinitis was higher among CW and WW compared to OW (p = 0.004). Significant differences among groups were observed in the questions «better weekend¼ (p < 0.034) and "improvement on vacation¼ (p < 0.000), in OASYS-2 Score (p < 0.000), in ABC Score (p < 0.000), and in methacholine score (p < 0.022). Rhinomanometry, FeNO, spirometry, and spirometry after bronchodilation had no significant differences among groups. Working conditions, ventilation system, work practice, use and type of mask revealed no significant differences.Conclusion: Asthma and rhinitis are significantly common among CW. Protective measurements used were not adequate to prevent asthma and or work related rhinitis. Early diagnosis might contribute to disease prevention and control.

Long-term exposure to ozone and children's respiratory health: Results from the RESPOZE study.

BACKGROUND: Although there is evidence on the effects of short-term ozone (O3) exposures on children's respiratory health, few studies have reported results on the effects of long-term exposures. We report the effects of long-term exposure to O3 on respiratory health outcomes in 10-11-year old children. METHODS: We conducted a panel study in a sample of the general population of school children in two cities with high average O3 concentrations, Athens and Thessaloniki, Greece. All 186 participating students were followed up intensively for 5 weeks spreading across a school year. Data was collected through questionnaires, weekly personal O3 measurements, spirometry, FeNO and time-activity diaries. Long-term O3 exposure was assessed using fixed site measurements and modeling, calibrated for personal exposures. The associations between measured lung function parameters and lung function growth over the study period, as well as FeNO and the occurrence of symptoms with long-term O3 exposure were assessed through the application of multiple mixed effects 2-level regression models, adjusting for confounders and for short-term exposures. RESULTS: A 10 µg/m3 increase in calibrated long-term O3exposure, using measurements from fixed site monitors was associated with lower FVC and FEV1 by 17 mL (95% Confidence Interval: 5-28) and 13 mL (3-21) respectively and small decreases in lung growth: 0.008% (0.002-0.014%) for FVC and 0.006% (0.000-0.012%) in FEV1 over the study period. No association was observed with PEF, FeNO or the occurrence of symptoms. A similar pattern was observed when the exposure estimates from the dispersion models were employed. CONCLUSIONS: Our study provides evidence that long-term O3 exposure is associated with reduced lung volumes and growth.

Comparison of diagnostic validity of mannitol and methacholine challenges and relationship to clinical status and airway inflammation in steroid-naïve asthmatic patients.

OBJECTIVES: The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical status, atopy and inflammation markers. METHODS: Eighty-eight patients, 47 women and 41 men, mean age 38.56 ± 16.73 years who presented with asthma related symptoms and were not on any anti-asthma medication, were challenged with mannitol and methacholine on separate days. Medical history regarding asthmatic symptoms, physical examination, skin prick tests and FeNO levels were also assessed. The clinical diagnosis of asthma was based on bronchodilator reversibility test. RESULTS: Sixty-seven patients were diagnosed with asthma and 21 without asthma. Both methacholine (P < 0.014) and mannitol (P < 0.000) challenges were significant in diagnosing asthma. The positive/negative predictive value was 93.33%/41.86% for methacholine, 97.72%/45.45% for mannitol and 97.05%/45.45%. for both methods assessed together. Worthy of note that 22% of asthmatics had both tests negative. There was a negative correlation between PC20 of methacholine and the FeNO level P < 0.001, and positive with the PD15 of mannitol P < 0.001 and the pre-test FEV1% pred P < 0.005, whereas PD15 of mannitol was negatively correlated with the FeNO level P < 0.001. Furthermore, dyspnea was the only asthmatic symptom associated with FeNO level P < 0.035 and the positivity of mannitol P < 0.014 and methacholine P < 0.04. CONCLUSIONS: Both challenge tests were equivalent in diagnosing asthma. Nevertheless, specificity appeared to be slightly higher in mannitol challenge.

Moxifloxacin pharmacokinetics and pleural fluid penetration in patients with pleural effusion.

The aim of this study was to evaluate the pharmacokinetics and penetration of moxifloxacin (MXF) in patients with various types of pleural effusion. Twelve patients with empyema/parapneumonic effusion (PPE) and 12 patients with malignant pleural effusion were enrolled in the study. A single-dose pharmacokinetic study was performed after intravenous administration of 400 mg MXF. Serial plasma (PL) and pleural fluid (PF) samples were collected during a 24-h time interval after drug administration. The MXF concentration in PL and PF was determined by high-performance liquid chromatography, and main pharmacokinetic parameters were estimated. Penetration of MXF in PF was determined by the ratio of the area under the concentration-time curve from time zero to 24 h (AUC24) in PF (AUC24PF) to the AUC24 in PL. No statistically significant differences in the pharmacokinetics in PL were observed between the two groups, despite the large interindividual variability in the volume of distribution, clearance, and elimination half-life. The maximum concentration in PF (CmaxPF) in patients with empyema/PPE was 2.23±1.31 mg/liter, and it was detected 7.50±2.39 h after the initiation of the infusion. In patients with malignant effusion, CmaxPF was 2.96±1.45 mg/liter, but it was observed significantly earlier, at 3.58±1.38 h (P<0.001). Both groups revealed similar values of AUC24PF (31.83±23.52 versus 32.81±12.66 mg·h/liter). Penetration of MXF into PF was similarly good in both patient groups (1.11±0.74 versus 1.17±0.39). Despite similar plasma pharmacokinetics, patients with empyema/parapneumonic effusion showed a significant delay in achievement of PF maximum MXF levels compared to those with malignant effusion. However, in both groups, the degree of MXF PF penetration and the on-site drug exposure, expressed by AUC24PF, did not differ according to the type of pleural effusion.

Bronchoalveolar lavage fluid and blood natural killer and natural killer T-like cells in cryptogenic organizing pneumonia.

BACKGROUND AND OBJECTIVE: Natural killer (NK) cells appear to be involved in the development of interstitial lung diseases (ILD). The purpose of this study was to investigate the involvement of NK and natural killer T (NKT)-like cells in two recognized cytotoxic ILD with systemic character, hypersensitivity pneumonitis (HP) and cryptogenic organizing pneumonia (COP), compared with idiopathic pulmonary fibrosis (IPF) and controls. METHODS: Bronchoalveolar lavage fluid (BALF) and peripheral blood (PBL) cells and lymphocyte subsets of 83 patients (26 with COP, 19 with HP and 38 with IPF) and 10 controls were prospectively studied by flow cytometry. RESULTS: The percentage of NK and NKT-like cells was lower in BALF than in PBL in all patient groups and controls. Patients with COP presented with statistically significantly higher NK and NKT-like cell counts in BALF compared with controls (P = 0.044 and P = 0.05 respectively) and IPF (P = 0.049 and P = 0.045 respectively). BALF NKT-like cell count correlated with PBL NKT-like cell count only in COP (r = 0.627, P = 0.002). In addition, a significant positive correlation between BALF NKT-like cell and PBL cytotoxic T CD8+ cell count was observed in COP (r = 0.562, P = 0.006) but not in HP, IPF or controls. CONCLUSIONS: Our study provides for the first time evidence for the implication of NKT-like cells in the pathogenesis of COP, as part of both localized and systemic cytotoxicity.

Is there a correlation between the changes in airway inflammation and the changes in respiratory mechanics after vaping in patients with asthma?

BACKGROUND: Electronic cigarettes (ECs) have been promoted as alternatives to traditional cigarettes. AIM: To investigate ECs' effects on respiratory system, especially in patients with respiratory diseases. METHODS: We randomly selected 25 smokers with stable moderate asthma and matched them with 25 healthy smokers. All were subjucted to pulmonary function tests (PFTs), impulse oscillometry (IOS), fraction exhaled Nitric Oxide (FeNO), exhaled breathe condensate (EBC) and biomarker measurements before and after vaping one nicotine-containing EC. RESULTS: The increase in FeNO 30 minutes after EC, reflecting airway inflammation, significantly correlated with increase of residual volume (RV), total lung capacity, respiratory impedance at 5 Hz (Z5Hz) and respiratory resistance at 5 and 20 Hz (R5Hz and R20Hz). No significant correlations were found between EBC biomarkers' changes and respiratory mechanics. CONCLUSION: This is the first study demonstrating that the changes in airway inflammation caused by EC have direct effects in respiratory mechanics of asthmatic patients.

NK cell populations in collagen vascular disease.

OBJECTIVES: Pulmonary involvement of varying etiology is common in collagen vascular diseases (CVDs). Bronchoalveolar lavage fluid (BALF) cell differentials reveal information on the immune mechanisms involved in the CVDs. The aim of the present study was to evaluate BALF cell populations in CVD-associated ILD and to investigate possible correlation with pulmonary function. METHODS: Fifty-seven patients (26 male and 31 female, mean age ± SD: 54.68±12.18 years) with CVD-associated interstitial lung disease were studied. Patients were divided into 6 groups based on underlying CVD. The study population also included a group of 10 healthy controls. BALF was examined in all individuals. Cell density, total cell number and differential cell count were recorded. BALF lymphocyte subsets were analysed by dual flow cytometry. Pulmonary function was assessed in all patients. RESULTS: BALF differential cell count did not differ significantly among the different groups. Scleroderma patients showed the highest percentage of CD19 cells (p<0.001). The NK and NKT cell percentages were significantly higher in systemic lupus erythematosus and in Sjögren, respectively, compared to other CVDs and controls (p=0.001 and p<0.001). Also BALF neutrophil percentage correlated negatively with FVC (r=-0.356, p=0.011) and FEV1 (r=-0.336, p=0.017) and BALF NKT cell percentage correlated negatively with pO2 (r=-0.415, p=0.003). CONCLUSIONS: Important variations observed in BALF cell populations suggest the implication of NK and NKT cells in the pathogenesis of lung involvement in CVDs.

BALF and BLOOD NK- cells in different stages of pulmonary sarcoidosis.

BACKGROUND AND OBJECTIVE: Data on natural killer (NK)- and natural killer T (NKT)- like cells in the immunopathogenesis of sarcoidosis remain limited. The aim was to assess NK- and NKT-like cells across different stages in bronchoalveolar lavage (BALF) versus peripheral blood (PB) in comparison to controls. METHODS: Forty four patients (32 women and 12 men, mean age 46.6±14.4 years) with biopsy-proven sarcoidosis and 10 healthy individuals (6 women, 4 men mean age 52.6±19.1 years) were submitted to BALF. Total cells and cell differentials were counted, while CD45+, CD3+, CD4+, CD8+, CD19+, CD3-CD16/56 (NK cells) and CD3+CD16/56+ (NKT-like cells) were determined by dual flow cytometry in BALF and PB. RESULTS: A significantly lower percentage of both NK and NKT-like cells was observed in BALF of controls and sarcoid patients (SP) compared to PB. Both BALF NK and NKT-cell counts were significantly higher in SP than in controls (NK: p=0.046, NKT-like: p=0.012) In addition BALF NK cell percentage differed among sarcoidosis stages (p=0.005). In PB NK-cell count was lower in sarcoidosis patients but the difference did not reach statistical significance. Also, in sarcoid patients' BALF NK-cell percentage negatively correlated with lymphocyte percentage (r=-0.962, p<0.001). CONCLUSIONS: The increased count of BALF NK and NKT-like cells in sarcoidosis compared to controls along with the increase of NK cells with stage progression are in line with a growing number of investigations suggesting the involvement of NK- and NKT-like cells in the pathogenesis of sarcoidosis.

Epidemiology of interstitial lung diseases and their progressive-fibrosing behaviour in six European countries.

The PERSEIDS study aimed to estimate incidence/prevalence of interstitial lung diseases (ILDs), fibrosing interstitial lung diseases (F-ILDs), idiopathic pulmonary fibrosis (IPF), systemic sclerosis-associated ILD (SSc-ILD), other non-IPF F-ILDs and their progressive-fibrosing (PF) forms in six European countries, as current data are scarce. This retrospective, two-phase study used aggregate data (2014-2018). In Phase 1, incident/prevalent cases of ILDs above were identified from clinical databases through an algorithm based on codes/keywords, and incidence/prevalence was estimated. For non-IPF F-ILDs, the relative percentage of subtypes was also determined. In Phase 2, a subset of non-IPF F-ILD cases was manually reviewed to determine the percentage of PF behaviour and usual interstitial pneumonia-like (UIP-like) pattern. A weighted mean percentage of progression was calculated for each country and used to extrapolate incidence/prevalence of progressive-fibrosing ILDs (PF-ILDs). In 2018, incidence/105 person-years ranged between 9.4 and 83.6 (ILDs), 7.7 and 76.2 (F-ILDs), 0.4 and 10.3 (IPF), 6.6 and 71.7 (non-IPF F-ILDs), and 0.3 and 1.5 (SSc-ILD); and prevalence/105 persons ranged between 33.6 and 247.4 (ILDs), 26.7 and 236.8 (F-ILDs), 2.8 and 31.0 (IPF), 22.3 and 205.8 (non-IPF F-ILDs), and 1.4 and 10.1 (SSc-ILD). Among non-IPF F-ILDs, sarcoidosis was the most frequent subtype. PF behaviour and UIP-like pattern were present in a third of non-IPF F-ILD cases each and hypersensitivity pneumonitis showed the highest percentage of progressive behaviour. Incidence of PF-ILDs ranged between 2.1 and 14.5/105 person-years, and prevalence between 6.9 and 78.0/105 persons. To our knowledge, PERSEIDS is the first study assessing incidence, prevalence and rate of progression of ILDs across several European countries. Still below the threshold for orphan diseases, the estimates obtained were higher and more variable than reported in previous studies, but differences in study design/population must be considered.

Asthma control test is correlated to FEV1 and nitric oxide in Greek asthmatic patients: influence of treatment.

BACKGROUND: Asthma is a common chronic disease affecting patients' health status and quality of life. Although recent guidelines focus on asthma control, asthma remains poorly controlled in many patients even under specialist care. Asthma Control Test™ (ACT) is a short, simple, patient-based tool that provides consistent assessment of asthma. OBJECTIVE: The aim of this study was to estimate the relationship of ACT with objective measures of lung function and inflammation such as forced expiratory volume in 1st second (FEV(1)) and exhaled nitric oxide (FeNO) in outpatients admitted for initial diagnosis of asthma and at follow-up. METHODS: One hundred and sixty (104 women and 56 men, mean age 39.7 ± 16.6 years) asthmatic patients with newly diagnosed asthma were included in the study. Patients completed the ACT questionnaire and underwent a detailed clinical examination, FeNO measurement, and prebronchodilator spirometry before (visit 1) and 4-12 weeks after initiation of treatment (visit 2). RESULTS: At visit 1, the mean ACT score was 21.27 ± 3.74. According to ACT score, 37 patients (23.1%) were completely controlled, 85 patients (53.1%) were partly controlled, and 38 patients (23.8%) were uncontrolled. Patients with uncontrolled asthma had statistically higher FeNO values than patients with partly controlled (p = .038) and completely controlled asthma (p = .016). ACT score was found to have a positive correlation with prebronchodilator %FEV(1) (r = 0.177, p = .025) and negative correlation with FeNO ( r = -0.211, p = .007). At visit 2, the mean ACT score was 23.00 ± 2.19. The change in ACT score between the two visits was significantly correlated to changes in FEV(1) (r = 0.538, p < .001) and in FeNO (r = -0.466, p < .001). Patients treated with inhaled corticosteroids (ICSs) showed significant improvement in FEV(1) and in ACT score and a decrease in FeNO compared with patients without ICS treatment. CONCLUSION: Although FEV(1) remains the main objective parameter for evaluating asthma, ACT score was found to reflect lung function and inflammation in a Greek asthmatic population.

Spirometry values in a Greek population: is there an appropriate reference equation?

BACKGROUND AND OBJECTIVE: Most published reference values for lung function test (LFT) parameters introduce systematic bias. The aim of this study was to compare measured values of FEV(1) and FVC with the corresponding normal predicted values in a Greek population, and to produce reference equations for LFT parameters in this population. METHODS: In a cross-sectional study conducted in Macedonia, Greece, 1080 adult healthy, non-smokers (432 men, 648 women, aged 18-80 years), underwent spirometry. Measured values of FVC and FEV(1) were compared with predicted values determined using three existing sets of reference equations: one recently derived from a European population and two others widely used in Europe (European Coal and Steel Community; ECSC) and the USA (National Health and Nutrition Examination Survey; NHANES III). Height and age were entered into the multivariate regression analysis to produce reference equations for LFT parameters. RESULTS: All three published sets of equations underpredicted FEV(1) in men. FVC was accurately predicted by all equations except NHANES III. The discrepancy was even greater among women; the ECSC equation underpredicted both FEV(1) and FVC, the NHANES III equation overpredicted both FEV(1) and FVC, while the third set of equations accurately predicted FEV(1) but overpredicted FVC. The derived reference equation for FEV(1) in men was -0.28 × age + 0.057 × height - 4.91, and in women -0.021 × age + 0.039 × height - 2.58. The derived reference equation for FVC in men was -0.28 × age + 0.071 × height - 6.763, and in women -0.019 × age + 0.056 × height - 5.018. CONCLUSIONS: Measured FEV(1) and FVC values in a Greek population differed significantly from those predicted using previously published reference equations. The new locally derived spirometry reference equations may be more suitable for evaluation of lung function in everyday practice.

Exercise capacity in idiopathic pulmonary fibrosis: the effect of pulmonary hypertension.

BACKGROUND AND OBJECTIVE: Increased pulmonary arterial pressure (PAP) usually coexists with impaired lung function in IPF. Data on the effect of pulmonary hypertension (PH) on cardiopulmonary responses during exercise in IPF patients is very limited. We sought to investigate the impact of PH on exercise capacity and the correlation between systolic PAP (sPAP) and pulmonary function testing, as well as cardiopulmonary exercise parameters, in patients with IPF and PH. METHODS: Eighty-one consecutive patients with IPF, who were evaluated over a 6-year period, were retrospectively studied. Patients underwent pulmonary function testing, Doppler echocardiography and maximal cardiopulmonary exercise testing. PH was defined as sPAP > 35 mm Hg. RESULTS: PH was diagnosed in 57% of the patients. Categorization of patients according to severity of PH indicated a significant reduction in maximum work rate, peak O(2) uptake, anaerobic threshold and peak O(2) pulse in those with sPAP > 50 mm Hg. In IPF patients with PH, estimated sPAP correlated with peak O(2) uptake, anaerobic threshold, peak O(2) pulse and end-tidal CO(2) at anaerobic threshold, while the strongest correlation was between sPAP and ventilatory equivalent for CO(2) at anaerobic threshold (r = 0.611, P < 0.001). There were no differences in pulmonary function or exercise parameters indicative of lung volume reduction, across the patient categories, and none of these parameters correlated with sPAP. CONCLUSIONS: PH has a negative impact on exercise capacity in IPF patients. In IPF patients with PH, resting sPAP correlated with exercise parameters indicative of gas exchange and circulatory impairment, but not with defective lung mechanics.

Pulmonary hypertension in idiopathic pulmonary fibrosis: a review.

Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse parenchymal disease with a poor prognosis. Pulmonary hypertension (PH) often complicates the course of IPF and may even be found in patients with preserved lung function. Possible pathogenetic mechanisms of PH in IPF include vascular destruction, pulmonary hypoxic vasoconstriction and vascular remodeling due to overexpression of cytokines and growth factors. PH in IPF patients is associated with decreased exercise capacity and a worse prognosis. Due to its prognostic significance, it seems important to investigate for PH in these patients. As the symptoms of PH in IPF are nonspecific, the development of PH in a patient with known IPF can be easily overlooked. Noninvasive methods provide clues for the diagnosis, but their sensitivity is limited. Doppler echocardiography is a useful tool for the detection of PH which also provides additional information regarding associated cardiac abnormalities. However, right heart catheterization remains the gold standard diagnostic test. Therapeutic options for PH in IPF are limited. Long-term oxygen administration for the correction of hypoxemia should be recommended. The availability of new pharmacological agents in the treatment of PH has raised the possibility of therapy in patients with IPF and associated PH. Whether these PH-targeted therapies may be of benefit in this patient group, in terms of improving functional outcomes and survival, remains uncertain.

Device use errors among patients with asthma and COPD and the role of training: a real-life study.

Background and objectives: Administration of inhaled medication for asthma and COPD is often difficult and incorrect device use is associated with unfavorable outcomes. We aimed to evaluate device use errors in asthma and COPD patients and to associate incorrect use with the patient's characteristics and medical history.Methods: Demographics and medical history were recorded. The use of each prescribed device was evaluated according to predefined steps.Results: 607 patients (49.9% male, median age (IQR) 63 (51, 70) years performed 663 demonstrations (56 patients were using 2 different types of devices). 51.4% were treated for asthma and 48.6% for COPD. 79.6% of demonstrations were performed using DPIs. Errors were documented on 41.2% of demonstrations and were associated with the type of device, p < 0.001. Elderly patients were less frequently using their devices correctly compared to younger patients, 50.8% vs 62.2%, respectively, p = 0.007. Correct demonstrations were more among asthmatics compared to COPD patients 63.1% vs 54.5%, p = 0.024. Incorrect use was associated with more acute exacerbations in the preceding year [median(IQR), 1(0, 2) vs 1(0, 1)], for incorrect and correct use, respectively, p < 0.001. Upon demonstration, 15.5% of patients have never been trained (i.e., undergone actual demonstrations and observation while using their device) by anyone. Errors occurred more frequently among patients who reported not to be trained compared to those who were trained, 67.0% vs 14.6%, respectively, p < 0.001. The commonest error was associated with the inspiration maneuver and accounted for the 48.3% of errors in the DPIs and 53.0% of errors in the MDIs.Conclusion: Device use errors are common and associated with unfavorable outcomes. Trained patients were more likely to use the device correctly.

Efficacy and safety of nintedanib in a Greek multicentre idiopathic pulmonary fibrosis registry: a retrospective, observational, cohort study.

Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). In a retrospective, real-world study across seven Greek hospitals, we evaluated the effectiveness and safety of nintedanib in routine clinical practice. Patients diagnosed with IPF, as per guideline criteria or multidisciplinary diagnosis, received nintedanib between January 2013 and January 2018. We evaluated 244 patients: mean±sd age 71.8±7.5 years, 79.1% male, 45.1% current smokers and 33.1% ex-smokers at treatment initiation. At baseline, predicted forced vital capacity (FVC) was 73.3±20.7% and predicted diffusing capacity of the lungs for carbon monoxide (D LCO) was 42.6±16.7%. On average, patients spent 23.6±15.0 months on nintedanib. At 3 years, 78 patients had died, equating to a 3-year survival rate of 59.4% (unaffected by treatment discontinuation or dose reduction). FVC% pred and D LCO% pred were largely stable at 3 years, with no significant difference from baseline (FVC 73.3±20.7% pred versus 78±20.1% pred, p=0.074; D LCO 42.6±16.7% pred versus 40.4±18.1% pred, p=0.334). Of the 244 patients, 55.7% reported an adverse event. Gastrointestinal events were the most common (173 (77.2%) out of 224 total events) and 45.0% of patients experienced diarrhoea. Only 32 (13.1%) patients had to permanently discontinue nintedanib due to an adverse event. This real-world study shows a 3-year survival rate of 59.4% and a low discontinuation rate due to adverse events. Our experience is consistent with previous findings in clinical trials of nintedanib in IPF.

Long-term prognosis of asthma is good--a 12-year follow-up study. Influence of treatment.

The number of studies on the prognosis of bronchial asthma (BA) is rather limited. The aim of the study was to determine the evolution of BA in a long-term 12-year follow-up and to investigate possible contributing factors. One hundred and sixty-three patients who visited the Out-patient Clinic for BA from 1989 to 1993 (Visit 1) were included in the study. They were re-evaluated during 2003-2005 (Visit 2). At both visits, the patients filled in a special questionnaire, underwent skin tests, spirometry, methacholine challenge and they were classified into three severity groups according to GINA of 1992 as: Mild, Moderate, and Severe asthma. At Visit 1, 95 (58.3%) patients were classified in the mild asthma group, 45 (27.6%) in moderate and 23 (14.1%) in severe; whereas at Visit 2, 107 (65.6%) patients had mild asthma, 44 (27%) moderate and 12 (7.4%) severe. At Visit 1 asthma severity was associated with male gender, younger age, and the absence of rhinitis. At Visit 2 on the other hand, asthma severity was associated with older age, longer duration of disease, smoking and again the absence of rhinitis and increased BHR at both visits. Inhaled corticosteroid use correlated with improvement in lung function. Long-term prognosis of BA was good and outcome was favorably influenced by male gender, early and mild onset of disease, absence of smoking and presence of rhinitis.

Th2/Th17 cytokine profile in phenotyped Greek asthmatics and relationship to biomarkers of inflammation.

OBJECTIVE: The aim of the present study was to investigate the Th2/Th17 pathway in asthmatic patients and also the relationship to asthma severity and biomarkers of inflammation. METHODS: 90 asthmatic patients, 51 patients with severe, 39 patients with mild asthma and 98 healthy controls were included. Skin prick tests, blood eosinophils, total serum IgE and exhaled FeNO were evaluated. Serum levels of IL-4, IL-5, IL-13, IL-6, IL-17A, IL-23 and TGFß1 were determined by Flow Cytometry using a panel kit (AimPlex Biosciences). The SNP of IL17A (rs17880588) was genotyped using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: The genotype of the SNP in IL17A (rs 17880588) was similar among all three groups. Serum levels of IL-4, IL-5, IL-13, IL-6, IL-17A and IL-23 were higher in asthmatics compared to controls (p < 0.05). In addition, IL-17A and IL-4 serum levels were found significantly elevated in patients with allergic asthma (p < 0.05). Furthermore, IL-4, IL-5, IL-13 and IL-23 were found significantly higher in patients with eosinophil cut off values above 300 cells/µl (p < 0.05). IL-17A levels were positively correlated with FeNO values in severe asthmatics with eosinophils>400 cells/µl. CONCLUSIONS: The above findings suggest the coexistence of Th2/Th17 pathway in severe, eosinophilic and in allergic asthma.

Epstein-Barr virus DNA in bronchoalveolar lavage fluid from patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis is the most common idiopathic interstitial pneumonia. The human herpesviruses and especially Epstein-Barr virus have been implicated in the etiology of idiopathic pulmonary fibrosis in a number of studies. AIM: The aim of this study was to investigate the potential association between idiopathic pulmonary fibrosis and Epstein-Barr virus. METHODS: Bronchoalveolar lavage fluid and sera were collected from 63 patients out of whom 17 suffered of idiopathic pulmonary fibrosis and 46 of other interstitial lung diseases. Sera from 50 healthy, age-matched individuals were also collected. Antibodies to the early, nuclear, and capsid antigens of Epstein-Barr virus were determined by enzyme immunoassay and indirect immunofluorescence. Additionally polymerase chain reaction was performed in bronchoalveolar lavage fluid in order to investigate the presence of Epstein-Barr virus DNA. Positive polymerase chain reaction results were confirmed by nucleotide sequencing. RESULTS: Statistically significant differences were observed in the frequency of IgA antibodies to viral capsid antigen among patients with idiopathic pulmonary fibrosis, patients with other interstitial lung diseases and healthy controls (60%, 24.4% and 22% respectively, p = 0.013). Epstein-Barr virus DNA was detected in the bronchoalveolar lavage fluid of 3 patients with idiopathic pulmonary fibrosis but in none of the patients with other diseases (p = 0.024). CONCLUSIONS: The results of this study support the association between IPF and EBV, at least in some cases, and provide evidence that BALF is an alternative for the detection of viral DNA in patients with IPF. However further investigation is required concerning the etiology of idiopathic pulmonary fibrosis.