Bronchiectasis is classically considered a neutrophilic disorder, but eosinophilic subtypes have recently been described.
To use multiple datasets available through the European Multicentre ...Bronchiectasis Audit and Research Collaboration to characterize eosinophilic bronchiectasis as a clinical entity focusing on the impact of eosinophils on bronchiectasis exacerbations.
Patients were included from five countries to examine the relationships between blood eosinophil counts and clinical phenotypes after excluding coexisting asthma. 16S rRNA sequencing was used to examine relationships between eosinophil counts and the sputum microbiome. A
analysis of the PROMIS (Inhaled Promixin in the Treatment of Non-Cystic Fibrosis Bronchiectasis) phase 2 trial was used to examine the impact of blood eosinophil counts on exacerbations in patients with
infection.
A relationship between sputum and blood eosinophil counts was demonstrated in two cohorts. In analysis of 1,007 patients from five countries, 22.6% of patients had blood eosinophil counts of ⩾300 cells/μl. Counts of <100 cells/μl were associated with higher bronchiectasis severity and increased mortality. There was no clear relationship with exacerbations. Blood eosinophil counts of ⩾300 cells/μl were associated with both
- and
-dominated microbiome profiles. To investigate the relationship of eosinophil counts with exacerbations after controlling for the confounding effects of infection, 144 patients were studied in a clinical trial after treatment with antipseudomonal antibiotics. Compared with patients with blood eosinophil counts of <100 cells/μl (reference), elevated eosinophil counts of 100-299 cells/μl (hazard ratio, 2.38; 95% confidence interval, 1.33-4.25;
= 0.003) and ⩾300 cells/μl (hazard ratio, 3.99; 95% confidence interval, 2.20-7.85;
< 0.0001) were associated with shorter time to exacerbation.
Eosinophilic bronchiectasis affects approximately 20% of patients. After accounting for infection status, raised blood eosinophil counts are associated with shortened time to exacerbation.
Bronchiectasis guidelines recommend long-term macrolide treatment for patients with three or more exacerbations per year without Pseudomonas aeruginosa infection. Randomised controlled trials suggest ...that long-term macrolide treatment can prevent exacerbations in adult patients with bronchiectasis, but these individual studies have been too small to do meaningful subgroup analyses. We did a systematic review and individual patient data (IPD) meta-analysis to explore macrolide benefit in subpopulations, including those in which macrolide therapy is not currently recommended.
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science from Jan 1, 2000, to Sept 30, 2018, to identify double blind, randomised, placebo-controlled trials of macrolide antibiotics in adult patients with bronchiectasis. We applied no language restrictions. Randomised controlled trials were eligible if treatment was defined a priori as long term and had a primary or secondary outcome of bronchiectasis exacerbations. Studies in patients with cystic fibrosis bronchiectasis were excluded. The primary outcome of the meta-analysis was frequency of exacerbations requiring treatment with antibiotics. Secondary endpoints were time to first exacerbation, change in quality of life according to the St George's Respiratory Questionnaire (SGRQ), and change in FEV
. IPD meta-analysis was done using fixed effects models adjusting for age, sex, FEV
, and trial. We did prespecified subgroup analyses for each of the primary and secondary endpoints using one-step meta-analysis only. Subgroups were defined by age, sex, previous exacerbation frequency, smoking status, inhaled corticosteroid use at baseline, body-mass index at baseline, cause, C-reactive protein at baseline, baseline FEV
percentage of predicted, SGRQ total score, and Pseudomonas aeruginosa in sputum culture at baseline. The meta-analysis is registered with the PROSPERO international register of systematic reviews, number CRD42018102908.
Of 234 identified studies, we included three randomised controlled trials, and IPD was obtained for 341 participants. Macrolide antibiotics reduced the frequency of exacerbations (adjusted incidence rate ratio IRR 0·49, 95% CI 0·36 to 0·66; p<0·0001). We also found that macrolide treatment improved the time to first exacerbation (adjusted hazard ratio 0·46, 0·34 to 0·61; p<0·0001) and was associated with improved quality of life measured by the SGRQ (mean improvement 2·93 points, 0·03 to 5·83; p=0·048). Macrolides were not associated with a significant improvement in FEV
(67 mL at 1 year, -22 to 112; p=0·14). Effect estimates in prespecified subgroup analyses revealed a reduced frequency of exacerbations in all prespecified subgroups, including a high level of benefit in patients with P aeruginosa infection (IRR 0·36, 0·18-0·72; p=0·0044) and in patients with one to two exacerbations per year (0·37, 0·16-0·88; p=0·025). Studies were rated as low risk of bias across all domains.
Long-term macrolide treatment significantly reduces the frequency of exacerbations in patients with bronchiectasis, with similar benefits observed in all subgroups based on patient characteristics. This finding suggests that macrolides might be considered in patients in whom macrolides are not indicated according to the current guidelines, particularly if alternative approaches to reduce exacerbations have been unsuccessful. However, downsides of long-term macrolide treatment must also be taken into account.
European Respiratory Society.
is the most commonly isolated pathogen in bronchiectasis and is associated with worse outcomes. Eradication treatment is recommended by guidelines, but the evidence base is limited. The expected ...success rate of eradication in clinical practice is not known.
We conducted a systematic review and meta-analysis according to Meta-Analysis of Observational Studies in Epidemiology guidelines. PubMed, Embase, the Cochrane Database of Systematic Reviews and Clinicaltrials.gov were searched for studies investigating
eradication treatment using antibiotics (systemic or inhaled) in patients with bronchiectasis. The primary outcome was the percentage of patients negative for
at 12 months after eradication treatment. Cystic fibrosis was excluded.
Six observational studies including 289 patients were included in the meta-analysis. Our meta-analysis found a 12-month
eradication rate of 40% (95% CI 34-45%; p<0.00001), with no significant heterogeneity (I
=0%). Combined systemic and inhaled antibiotic treatment was associated with a higher eradication rate (48%, 95% CI 41-55%) than systemic antibiotics alone (27%, 13-45%).
Eradication treatment in bronchiectasis results in eradication of
from sputum in ∼40% of cases at 12 months. Combined systemic and inhaled antibiotics achieve higher eradication rates than systemic antibiotics alone.
After having traveled to California in 2017, a 26-year old Dutch man presented in 2020 with persisting cough and shortness of breath. Radiology showed cystic bronchiectasis with peri-bronchial ...consolidation in his right upper lobe. Laboratory studies in August 2021 showed an increased total IgE, specific Aspergillus IgE, eosinophilia and positive BAL culture for Coccidioides immitis/posadasii. After 6 weeks of itraconazole treatment for suspected allergic bronchopulmonary aspergillosis, symptoms persisted and respiratory cultures remained positive. The infection was cleared after a 6-month course of fluconazole. (max 75 words)
Abstract
Background
Use of long-term tobramycin inhalation solution (TIS) has been shown beneficial in cystic fibrosis (CF) and earlier findings also suggest a benefit in non-CF bronchiectasis. We ...investigated the efficacy and safety of maintenance TIS once daily (OD) in frequent exacerbating bronchiectasis patients chronically infected by different pathogens sensitive for tobramycin.
Objective
The primary outcome was the frequency of exacerbations during the 12-month study period. Secondary outcomes were time to first exacerbation, change in lung function and quality of life (QoL), bacterial analysis and safety.
Materials/patients
In this multicenter RCT patients aged ≥ 18-year-old were included with confirmed bronchiectasis and ≥ 2 exacerbations in the preceding year. Patients were assigned (1:1) to receive TIS or placebo OD for 1-year.
Results
58 patients were included of which 52 were analyzed in the mITT analysis. TIS reduced exacerbation frequency with a RR of 0.74 (95% CI 0.49–1.14) (
p
= 0.15). Within the TIS population a decrease in number of exacerbations was found (2;
p
= 0.00), which was also seen in the placebo-treated patients (1.5;
p
= 0.00). In the TIS-treated patients the QoL improved (LRTI-VAS
p
= 0.02 Leicester Cough
p
= 0.02) without additional safety concerns. No differences were found for the other secondary outcomes.
Conclusion
Long-term TIS OD is a safe treatment modality and showed a non-significant reduced exacerbation frequency of 0.74 as compared to placebo in bronchiectasis patients chronically infected by tobramycin sensitive pathogens. TIS OD may be a potential therapeutic strategy in selected patients with bronchiectasis suffering from a high burden of disease.
Trail registration number:
The BATTLE study was registered at Clinical trials.gov number:
NCT02657473
. Date: 13 august 2016.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Primary ciliary dyskinesia (PCD) might be a risk factor for the development of anxiety and depression. This study investigated the associations between anxiety, depression and health-related quality ...of life (HRQoL) in individuals with PCD and their caregivers.
Children, adolescents and adults with PCD and their caregivers were invited to participate in a mental health screening programme. During regular yearly outpatient visits, measures of anxiety (GAD-7), depression (PHQ-9), HRQoL (QOL-PCD), lung function (forced expiratory volume in 1 s (FEV
)) and body mass index (BMI)) were collected and associations of anxiety, depression and HRQoL were estimated.
A total of 103 individuals participated in the mental health screening programme. Elevated levels of anxiety (scores ≥10 on GAD-7) were found in 6% of adults (n=33), 14% of children (n=7), 6% of adolescents (n=17) and 20% of caregivers (n=46, 52% of mothers). Elevated depression levels (scores ≥10 on PHQ-9) were found in 18% of adults, 14% of children, 6% of adolescents and 11% of caregivers. Anxiety and depression were associated with scales on the QOL-PCD. Mothers reported higher anxiety scores than fathers (30%
9%, p=0.03). A strong negative relationship was found between depression in caregivers and physical functioning (QOL-PCD) of the child. Anxiety and depression were not significantly associated with anxiety/depression in their child.
This is the first study investigating anxiety and depression in individuals with PCD and their caregivers. Our results revealed elevated levels of anxiety and depression, which were associated with worse HRQoL. These results suggest the need for psychological support in PCD.
Elexacaftor/tezacaftor/ivacaftor (ETI) is a cystic fibrosis (CF) transmembrane conductance regulator modulator, which has shown efficacy in CF patients (≥6 years) with ≥1 Phe508del mutation and a ...minimal function mutation. In October 2019, ETI became available on compassionate use basis for Dutch CF patients with severe lung disease. Our objective was to investigate safety and efficacy of ETI in this patient group in a real‐life setting. A multicenter longitudinal observational study was conducted to examine changes in FEV1, BMI, and adverse events at initiation and 1, 3, 6, and 12 months after starting ETI. The number of exacerbations was recorded in the 12 months before and the 12 months after ETI treatment. Patients eligible for compassionate use had a FEV1 <40% predicted. Wilcoxon signed‐rank test analyzed changes over time. Twenty subjects were included and followed up for up to 12 months after starting ETI. Treatment was well tolerated with mild side effects reported, namely, rash (15%) and stomach ache (20%) with 80% resolving within 1 month. Mean absolute increase of FEV1 was 11.8/13.7% (p ≤ .001) and BMI was 0.49/1.87 kg/m2 (p < .001–0.02) after 1/12 months, respectively. In comparison to the number of exacerbations pretrial, there was a marked reduction in exacerbations after initiation. Our findings show long‐term effects of treatment with ETI in patients with severe CF lung disease in a real‐life setting. Treatment with ETI is associated with increased lung function and BMI, less exacerbations, and only mild side effects.
Elexacaftor/tezacaftor/ivacaftor (ETI) is effective in a real‐life setting with severe cystic fibrosis lung disease patients. The effect maintains for up to 12 months and the treatment was well tolerated and reduced the number of exacerbations. Sputum production is significantly lower after ETI initiation.
Targeted cystic fibrosis (CF) therapy with lumacaftor/ivacaftor partly restores chloride channel function and improves epithelial fluid transport in the airways. Consequently, changes may occur in ...the microbiome, which is adapted to CF lungs.
To investigate the effects of lumacaftor/ivacaftor on respiratory microbial composition and microbial metabolic activity by repeatedly sampling the lower respiratory tract.
This was a single-centre longitudinal observational cohort study in adult CF patients with a homozygous Phe508del mutation. Lung function measurements and microbial cultures of sputum were performed as part of routine care. An oral and nasal wash, and a breath sample, were collected before and every 3 months after starting therapy, for up to 12 months.
Twenty patients were included in this study. Amplicon 16S RNA and metagenomics sequencing revealed that
was most abundant in sputum and seemed to decrease after 6 months of treatment, although this did not reach statistical significance after correction for multiple testing. Two types of untargeted metabolomics analyses in sputum showed a change in metabolic composition between 3 and 9 months that almost returned to baseline levels after 12 months of treatment. The volatile metabolic composition of breath was significantly different after 3 months and remained different from baseline until 12 months follow-up.
After starting CF transmembrane conductance regulator (CFTR) modulating treatment in CF patients with a homozygous Phe508del mutation, a temporary and moderate change in the lung microbiome is observed, which is mainly characterised by a reduction in the relative abundance of
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