Continuous alternating inhaled antibiotic therapy in CF: A single center retrospective analysis.

INTRODUCTION: The efficacy of inhaled antibiotics to treat chronic Pseudomonas aeruginosa pulmonary infection in patients with cystic fibrosis (CF) has been well established. Few data are available on the value of continuous alternating inhaled antibiotic therapy (CAIT), a strategy increasingly used in the management of CF. OBJECTIVE: To investigate the effect of CAIT on clinical outcome in adult CF patients treated at the University Hospital Leuven. METHODS: Patients with a documented CF diagnosis who received inhaled antibiotics between March 2010 and January 2015 were retrospectively evaluated. In patients receiving CAIT patient characteristics, recorded spirometry data and number of IV antibiotic days were collected retrospectively at fixed time intervals, from 6months before to one year after the start of the 2nd inhaled antibiotic. For patients on inhaled antibiotic monotherapy (IAMT), the same data were obtained at similar intervals during the study period. RESULTS: A total of 49 of 89 patients using chronic inhaled antibiotic therapy received CAIT. Patients receiving CAIT had a lower baseline FEV1 and were more likely to be homozygous for F508del compared to patients receiving IAMT. FEV1 deteriorated on average by a factor of 0.904 per year (95% CI: 0.851-0.960) prior to the start of CAIT. The initiation of CAIT was associated with an average improvement in FEV1 by a factor of 1.148 per year (95% CI: 1.068-1.236, p=0.0002). The analysis of specific types of antibiotics revealed evidence of positive effects of adding COLI to TOBI and COLI to AZLI. We found no effect of the initiation of CAIT on the number of IV antibiotic days (p=0.80). CONCLUSION: CF patients with more advanced lung disease are more likely to receive CAIT. In this patient group, CAIT was associated with a significant improvement in FEV1. Further data are warranted to identify the value of CAIT.

Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts.

INTRODUCTION: Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. METHODS: We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. RESULTS: The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. CONCLUSION: The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity.

Genetic variation in immunoglobulin G receptor affects survival after lung transplantation.

Chronic rejection remains the most important complication after lung transplantation (LTx). There is mounting evidence that both rheumatoid arthritis and chronic rejection share similar inflammatory mechanisms. As genetic variants in the FCGR2A gene that encodes the immunoglobulin gamma receptor (IgGR) have been identified in rheumatoid arthritis, we investigated the relationship between a genetic variant in the IgGR gene and chronic rejection and mortality after LTx. Recipient DNA from blood or explant lung tissue of 418 LTx recipients was evaluated for the IgGR (rs12746613) polymorphism. Multivariate analysis was carried out, correcting for several co-variants. In total, 216 patients had the CC-genotype (52%), 137 had the CT-genotype (33%) and 65 had the TT-genotype (15%). Univariate analysis demonstrated higher mortality in the TT-genotype compared with both other genotypes (p < 0.0001). Multivariate analysis showed that the TT-genotype had worse survival compared with the CC-genotype (hazard ratio [HR] = 2.26, p = 0.0002) but no significance was observed in the CT-genotype (HR = 1.32, p = 0.18). No difference was seen for chronic rejection. The TT-genotype demonstrated more respiratory infections (total, p = 0.037; per patient, p = 0.0022) compared with the other genotypes. A genetic variant in the IgGR is associated with higher mortality and more respiratory infections, although not with increased prevalence of chronic rejection, after LTx.

Mortality in non-cystic fibrosis bronchiectasis: a prospective cohort analysis.

INTRODUCTION: There is limited data on mortality and associated morbidity in non-cystic fibrosis bronchiectasis (NCFB). Our aim was to analyze the overall mortality for all newly diagnosed patients from June 2006 onwards and to evaluate risk factors for mortality in this cohort. METHODS: 245 patients who had a new diagnosis of NCFB between June 2006 and October 2012 at the University Hospital of Leuven, Belgium, were included in the analysis. Death was analyzed until end of November 2013. All patients had chest HRCT scan confirming the presence of bronchiectatic lesions and had symptoms of chronic productive cough. Univariate and multivariate Cox proportional hazard survival regression analysis was used to estimate hazard ratios (HR) and their 95% confidence intervals (CI) of variables possibly predicting mortality. RESULTS: Overall mortality in NCFB patients who had a median follow-up of 5.18 years was 20.4%. Patients with NCFB and associated chronic obstructive pulmonary disease (COPD) had a mortality of 55% in that period. Univariate analysis showed higher mortality according to age, gender, smoking history, Pseudomonas aeruginosa status, spirometry, radiological extent, total number of sputum bacteria and underlying etiology. Multivariate analysis showed significant higher mortality with increasing age (HR = 1.045; p = 0.004), with increasing number of lobes affected (HR = 1.53; p = 0.009) and when patients had COPD associated NCFB (HR = 2.12; p = 0.038). The majority of the 50 deaths were respiratory related (n = 29; 58%). CONCLUSION: NCFB patients with associated COPD disease had the highest mortality rates compared to the other NCFB patients. Additional risk factors for lower survival were increasing age and number of lobes affected.

Papain-induced asthma: a man with dyspnea from dawn till dust.

A 52-year-old man, a current smoker (40 pack years) with unremarkable medical history, was referred to the outpatient pneumology clinic because of recent complaints of shortness of breath and wheezing, which were relieved by inhaled bronchodilators. Serial peak expiratory flow (PEF) measurements showed a clear rise in PEF during the weekend and a fall on the evening after the first day of the week. It also showed that evening values were always lower than morning values. During a holiday, a slow but persistent rise in PEF was observed. Such a pattern is highly suggestive for occupational asthma. A detailed description of his job revealed papain exposure. After a positive specific IgE and skin prick test for papain the diagnosis of papain induced asthma was made. When an allergy and serious lung function impairment is proven against products encountered in a work related situation, not improving after maximal preventive measures, the patient is advised to change job.

Effect of macrolide on lung function and computed tomography (CT) score in non-cystic fibrosis bronchiectasis.

BACKGROUND: The few studies addressing the effect of macrolides in non-cystic fibrosis bronchiectasis (NCFB) range from no decline to significant improvement. There are no data evaluating macrolides on CT score. OBJECTIVES: To retrospectively evaluate the effect of initiation of macrolides on spirometry and HRCT in a NCFB population. METHODS: We performed a word search in the electronic patient file data of the University Hospital of Leuven, Belgium, identifying all NCFB patients observed during a 41 month period and treated with macrolides. Records of all NCFB patients were manually reviewed, evaluating spirometry and CT scans, before and after/during macrolide treatment, treatment scheme, Pseudomonas status and other relevant data. CT scoring was done by using a modified version of the Brody score. RESULTS: Evaluation of 131 patients showed a mean FEV1 improvement of 185 ml (p<0.0001) or 7.7% (p<0.0001) and a mean FVC improvement by 234 ml (p<0.001) or 7.4% (p<0.001). Smoking history, gender, Pseudomonas colonization and baseline lung function did not affect improvement in lung function. Patients with NCFB due to an immunodeficiency showed a significant larger macrolide-associated improvement in FEV1% (p=0.0075) and FVC% (p=0.0063) than patients with NCFB due to other causes. An improvement was noted in CT subscores for bronchiectasis (p=0.0053), mucus plugging (p=0.0256), peribronchial thickening (p=0.0037), parenchyma (p=0.026) and total modified Brody score (p=0.001) after versus before macrolide therapy. CONCLUSION: Macrolides, as part of a multimodal and individualized therapy may significantly improve FVC, FEV1 and the modified Brody score in patients with NCFB, especially those with NCFB due to immunodeficiency.

Higher food intake and appreciation with a new food delivery system in a Belgian hospital. Meals on Wheels, a bedside meal approach: a prospective cohort trial.

AIM: A new system of meal distribution called Meals on Wheels, allowing food ordering at mealtime and providing guidance by trained nutritional assistants, might show benefit in offering nutritional support. This study investigates whether Meals on Wheels improves total food intake per day and yielded improved appreciation of food quality and increased access to food and mealtimes. METHODS: In a prospective cohort trial where control and intervention groups were taken from all patients hospitalized at the respiratory disease department, age, sex, BMI, admission weight, height, reason for admission and discharge weight were noted, as was food intake, supplements, waste per meal and daily total. For food appreciation the questionnaire developed by Naithani et al. was used. The study included 83 patients in the control group and 106 patients in the Meals on Wheels group. RESULTS: Mean total daily food intake was 236 g higher in patients in the Meals on Wheels than in controls. There was higher intake of oral nutritional supplements in the Meals on Wheels group compared to controls, resulting in significantly less oral nutritional supplements wasted. There was also significantly less waste in the Meals on Wheels group. For food access and appreciation, patients appreciated Meals on Wheels more than the old system in terms of choice, hunger, food quality and organization. CONCLUSIONS: Meals on Wheels resulted in higher food intake during each meal, less waste and better use of oral nutritional supplements. Patients appreciated Meals on Wheels more than the old system in terms of choice, hunger, food quality and organization.