Drug compounds that augment the production and activity of the cystic fibrosis (CF) transmembrane regulator (CFTR) have revolutionised CF care. Many adults and some children with CF suffer advanced ...and severe lung disease or await lung transplantation. While the hope is that these drug compounds will prevent lung damage when started early in life, there is an ongoing need to care for people with advanced lung disease. The focus of this review is the accumulating data from clinical trials and case series regarding the benefits of CFTR modulator therapy in people with advanced pulmonary disease. We address the impact of treatment with ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor and elexacaftor/tezacaftor/ivacaftor on lung function, pulmonary exacerbations, nutrition and quality of life. Adverse events of the different CFTR modulators, as well as the potential for drug-drug interactions, are discussed.
is responsible for chronic infection in many bronchiectasis patients but it is not known whether it is associated with worse clinical outcomes independent of the underlying severity of disease.This ...study analysed data from 2596 bronchiectasis patients included from 10 different bronchiectasis clinical centres across Europe and Israel, with a 5-year follow-up period. Prevalence of
chronic infection and its independent impact on exacerbations, hospitalisations, quality of life and mortality was assessed.The prevalence of
chronic infection was 15.0% (n=389).
was associated with a higher mortality in a univariate analysis (hazard ratio (HR) 2.02; 95% (confidence interval) CI 1.53-2.66; p<0.0001) but an independent impact on mortality was not found in a multivariate analysis (HR 0.98; 95% CI 0.70-1.36; p=0.89).
was independently associated with increased mortality only in patients with frequent exacerbations (two or more per year) (HR 2.03; 95% CI 1.36-3.03; p=0.001). An independent association with worse quality of life of 7.46 points (95% CI 2.93-12.00; p=0.001) was found in a multivariable linear regression.
was therefore found to be independently associated with exacerbation frequency, hospital admissions and worse quality of life. Mortality was increased in patients with
particularly in the presence of frequent exacerbations.
Bronchiectasis is a clinical and radiological diagnosis associated with cough, sputum production and recurrent respiratory infections. The clinical presentation inevitably overlaps with other ...respiratory disorders such as asthma and chronic obstructive pulmonary disease (COPD). In addition, 4-72% of patients with severe COPD are found to have radiological bronchiectasis on computed tomography, with similar frequencies (20-30%) now being reported in cohorts with severe or uncontrolled asthma. Co-diagnosis of bronchiectasis with another airway disease is associated with increased lung inflammation, frequent exacerbations, worse lung function and higher mortality. In addition, many patients with all three disorders have chronic rhinosinusitis and upper airway disease, resulting in a complex "mixed airway" phenotype.The management of asthma, bronchiectasis, COPD and upper airway diseases has traditionally been outlined in separate guidelines for each individual disorder. Recognition that the majority of patients have one or more overlapping pathologies requires that we re-evaluate how we treat airway disease. The concept of treatable traits promotes a holistic, pathophysiology-based approach to treatment rather than a syndromic approach and may be more appropriate for patients with overlapping features.Here, we review the current clinical definition, diagnosis, management and future directions for the overlap between bronchiectasis and other airway diseases.
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 (BE) is a chronic and progressive respiratory disease with multiple possible causes 1, 2. Many require a specific therapy and thus, a systematic aetiologic evaluation is recommended by ...guidelines 3. Studies have shown wide heterogeneity in the proportion of different aetiologies identified among centres 4–8, which can be partially justified because of geographical risks factors, but may also reflect variations in testing practice or in the definitions of aetiology used 9. The proportion of patients classified as idiopathic varies (26–74%) across the literature, and this variability is likely to be somewhat linked to a lack of use of a standard aetiological algorithm 4–8.
The incidence of nontuberculous mycobacteria (NTM) infection among people with bronchiectasis varies between different geographical areas and accordingly between different series 1, 2. Studies are ...largely based on bronchiectasis referral centres, which routinely screen for NTM in respiratory secretions. Therefore, the reported estimates of NTM prevalence in bronchiectasis may be exaggerated. Studies from bronchiectasis centres show conflicting results regarding risk factors for NTM: older age was found to increase risk in some but not other centres 1–4. Due to the small numbers of patients in these studies, it is usually not possible to determine the effect of NTM infection on prognosis.
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.
Summary Background The term “obesity paradox”, refers to lower mortality rates in obese patients, and is evident in various chronic cardiovascular disorders. There is however, only scarce data ...regarding the clinical implication of obesity and pulmonary hypertension (PH). Therefore, in the current study, we evaluated the possible prognostic implications of obesity in PH patients. Methods We assessed 105 consecutive PH patients for clinical and hemodynamic parameters, focusing on the possible association between Body Mass Index (BMI) and mortality. Follow-up period was 19 ± 13 months. Results Sixty-one patients (58%) had pre-capillary PH and 39 patients (37%) out-of-proportion post-capillary PH. During follow-up period, 30 patients (29%) died. Death was associated with reduced functional-class, inverse-relation with BMI, higher pulmonary artery and right atrial pressures, pulmonary vascular resistance and signs of right ventricular failure. In multivariate analysis, obesity (BMI ≥ 30 kg/m²), was the variable most significantly correlated with improved survival H.R 0.2, 95% C.I 0.1–0.6; p = 0.004, even after adjustment for baseline characteristics. Obese and very-obese (BMI ≥ 35 kg/m²) patients had significantly less mortality rates during follow-up (12% and 8%, respectively) than non-obese patients (41%), p = 0.01. The tendency of survival benefit for the obese vs. non-obese patients was maintained both in the pre-capillary (10% vs. 46% mortality, p = 0.008) and disproportional post-capillary PH patients (11% vs. 40% mortality, p = 0.04). Conclusions Obesity was significantly associated with lower mortality in both pre-capillary and disproportional post-capillary PH patients. It seems that in PH, similarly to other chronic clinical cardiovascular disease states, there may be a protective effect of obesity, compatible with the “obesity paradox”.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Is bronchiectasis really a disease? Shteinberg, Michal; Flume, Patrick A; Chalmers, James D
European respiratory review,
03/2020, Volume:
29, Issue:
155
Journal Article
Peer reviewed
Open access
The definition of a disease requires that distinguishing signs and symptoms are present that are common, and that the constellation of signs and symptoms differentiate the condition from other ...causes. In bronchiectasis, anatomical changes, airways inflammation and airway infection are the distinguishing features that are common to this disease. However, bronchiectasis is a heterogenous disease: signs and symptoms are shared with other airway diseases, there are multiple aetiologies and certain phenotypes of bronchiectasis have distinct clinical and laboratory features that are not common to all people with bronchiectasis. Furthermore, response to therapeutic interventions in clinical trials is not uniform. The concept of bronchiectasis as a treatable trait has been suggested, but this may be too restrictive in view of the heterogeneity of bronchiectasis. It is our opinion that bronchiectasis should be defined as a disease in its own right, but one that shares several pathophysiological features and "treatable traits" with other airway diseases. These traits define the large heterogeneity in the pathogenesis and clinical features and suggest a more targeted approach to therapy.
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