Moderate Bronchiectasis Research Articles

Characteristics of different pathogenic bacterial infections and their effects on prognosis in adult patients with bronchiectasis.

The present study aimed to analyse the types of pathogens infecting adults with bronchiectasis and the effects of different pathogens on the number of acute exacerbations and the length of hospitalization for 1 year in patients with severe bronchiectasis. A total of 522 patients with bronchiectasis admitted to the Department of Respiratory and Critical Care Medicine at the Second Hospital of Jiaxing (Zhejiang, China) between January 2019 and December 2022 were retrospectively analysed. The patients were divided into a mild to moderate group and a severe group according to the bronchiectasis severity index criteria. The basic and clinical information of all the patients was collected. The patients were followed up for 1 year after the day when the sputum or alveolar lavage fluid samples tested positive for pathogens. The follow-up information included the exacerbation of cough symptoms, the number of hospitalizations and the number of days of antibiotic use in patients with bronchiectasis. A total of 522 patients with bronchiectasis were positive for pathogens, including 192 patients with Pseudomonas aeruginosa (P. aeruginosa; 36.8%), 60 patients with Klebsiella pneumoniae (K. pneumoniae; 11.5%), 48 patients with mixed pathogens (≥2 pathogens at the same time; 9.2%), 36 patients with Staphylococcus aureus (6.9%), 33 patients with Aspergillus fumigatus (6.3%), 30 patients with Haemophilus influenzae (5.7%), 15 patients with Acinetobacter baumannii (A. baumannii; 2.9%) and 108 patients with other pathogens (20.7%). Compared with patients with mild to moderate bronchiectasis, patients with severe bronchiectasis were more likely to have P. aeruginosa but less likely to have K. pneumoniae and other pathogens. The length of hospitalization and duration of antibiotic use in the severe group of patients with bronchiectasis caused by P. aeruginosa, A. fumigatus, or A. baumannii were significantly longer than those in the mild to moderate group. During the 1-year follow-up, the number of acute exacerbations and hospitalizations of patients with severe bronchiectasis caused by A. baumannii and P. aeruginosa were significantly greater than those of patients with severe bronchiectasis caused by other pathogens. According to logistic regression analysis, A. baumannii and P. aeruginosa were independent risk factors for acute exacerbation of severe bronchiectasis in the following year. In patients with severe bronchiectasis, the pathogens A. baumannii, P. aeruginosa and A. fumigatus were independent risk factors for future acute exacerbations and increased risk of hospitalization.

Research of the diagnostic utility of impulse oscillometry in patients with bronchiectasis

Background: Bronchiectasis is a chronic respiratory condition in which infection, inflammation, and damage of the airways all play a role. Intense airway inflammation is precipitated by pathogenic insults, resulting in chronic airway damage. Impulse oscillometry (IOS) is a noninvasive approach that might offer worldwide information on airway resistance by researching the mechanical waves superimposed upon breathing movements. It has been observed that IOS may differentiate peripheral airways abnormalities in chronic obstructive pulmonary disease (COPD), asthma, interstitial pulmonary disease (ILD) and pulmonary fibrosis (CF) with high degree of precision. Methods: This research was carried out on 40 cases with bronchiectasis diagnosed by HRCT. Such cases were classified into two groups, according to Bronchiectasis Severity Index (BSI)(108): group I: Included 20 cases with mild to moderate bronchiectasis and group II: Included 20 cases with severe bronchiectasis. Cases included in the research were subjected to full history taking and complete physical examination. This includes: Complete blood count (CBC), sputum culture, chest x-ray to exclude cases with other lung diseases, High-Resolution Computerized Tomography (HRCT), that were interpreted for the presence, pattern and distribution of bronchiectasis, arterial blood gases, echocardiography, measuring systolic pulmonary artery pressure, pulmonary function tests (PFT), Impulse Oscillometry and reactance area (AX) were measured. Results: Regarding disease duration, no significant differences was found between both groups while a statistically significant difference was observed between groups regarding the used medications. Regarding laboratory investigations, no significant difference was observed among the groups for any of the measured measurements. Regarding functional assessment data, A statistically evident difference was found between groups in the following: MEF 50%, FEV1% predicted, FEV1/FVC% and FVC% with no significant differences in FEV1. Regarding IOS measurements, A statistically evident difference was found between both groups in R5% predicted while no difference was observed regarding R5 actual, R20, AX, or X5. Positive correlation was very high in between HRCT score and each of FEV1% predicted, FVC (%) AX, R5% predicted, R5 actual, R20 and X5 but negative correlation was very high in between HRCT score and MEF 75%, FEV1/FVC% Conclusions: IOS measurements are markedly increased in cases with bronchiectasis and they are correlated with spirometric measurements and HRCT scores.

The effect of a training webinar on decreasing inter-observer variability in making a radiologic diagnosis of bronchiectasis

Non-cystic fibrosis bronchiectasis is a clinically important disease with an estimated 340,000–522,000 persons living with the disease and 70,000 being diagnosed annually. The radiographic diagnosis remains a pivotal part of recognizing the disease due to its protean clinical manifestations. As physicians are sensitized to this disease, a greater proportion of patients are being diagnosed with mild to moderate bronchiectasis. Despite the established use of CT chest as the main tool for making a radiologic diagnosis of bronchiectasis, the literature supporting the process of making that diagnosis is somewhat sparse. Concurrently, there has been an increased trend to have Web-based radiologic tutorials due to its convenience, the ability of the learner to set the pace of learning and the reduced cost compared to in-person learning. The COVID-19 pandemic has accelerated this trend. We wanted to look carefully at the effect of a Web-based training session on interrater reliability. Agreement was calculated as percentages and kappa and prevalence adjusted kappa calculated. We found that a single Web-based training session had little effect on the variability and accuracy of diagnosis of bronchiectasis. Larger studies are needed in this area with multiple training sessions.

Cardiovascular and cerebrovascular-associated mortality in patients with preceding bronchiectasis exacerbation.

Bronchiectasis is associated with an increased incidence of atherosclerotic cardiovascular disease (ASCaVD) and atherosclerotic cerebrovascular disease (ASCeVD). Its effect on associated mortality is unclear. This study investigated the effects of bronchiectasis exacerbation prior to ASCaVD or ASCeVD events on mortality in patients with bronchiectasis using a large population-based database. A retrospective cohort of patients with bronchiectasis who experienced ASCaVD (n = 1066) or ASCeVD (n = 825) was studied for the first time using a nationwide population-based database (National Health Insurance Service-National Sample Cohort, Korea, 2002-2015). We classified each cohort according to the presence of moderate bronchiectasis exacerbation within 1 year before the ASCaVD or ASCeVD event. We evaluated 90-day, 1-year, and all-cause mortalities risk. Within 1 year before the index ASCaVD or ASCeVD event, 149 (13.9%) and 112 (13.6%) patients with bronchiectasis experienced moderate exacerbation(s), respectively. Mild exacerbations did not different in frequency between the survivors and nonsurvivors. In both cohorts, more nonsurvivors experienced moderate exacerbations than survivors. The odds ratios of 90-day and 1-year mortalities and hazard ratios of all-cause mortalities on experiencing moderate exacerbations were 2.27 [95% confidence interval (CI) = 1.26-4.10], 3.30 (95% CI = 2.03-5.38), and 1.78 (95% CI = 1.35-2.34) in the bronchiectasis-ASCaVD cohort and 1.73 (95% CI = 0.94-3.19), 1.79 (95% CI = 1.07-3.00), and 1.47 (95% CI = 1.10-1.95), in the bronchiectasis-ASCeVD cohort. Hospitalization or emergency room visit for bronchiectasis exacerbation within 1 year before ASCaVD or ASCeVD is associated with an increased ASCaVD- or ASCeVD-associated mortality.

Dysregulation of prostaglandins, leukotrienes and lipoxin A4 in bronchiectasis

IntroductionBronchiectasis is characterised by excessive neutrophilic inflammation. Lipid mediators such as prostaglandins and leukotrienes have crucial roles in the inflammatory response. Further characterisation of these lipids and understanding the interplay...

Utility of Bronchiectasis severity index (BSI) as prognostic tool in patients with post tubercular bronchiectasis: An experience from a tertiary care hospital in North India

BackgroundBronchiectasis severity Index (BSI) score which predicts the severity of the disease along with future exacerbations and mortality rate has been well validated in European patients; however there is paucity of data evaluating its validity in Indian patients. The authors therefore decided to evaluate the utility of BSI to predict exacerbations and mortality rate in patients with post tubercular bronchiectasis presenting to our facility. MethodsThe study was a retrospective observational study done in patients with bronchiectasis secondary to tuberculosis. These patients were followed up for 4 years. BSI was calculated from different variables and descriptive statistics along with regression analysis were used to evaluate utility of BSI. ResultsA total of 48 patients of post tubercular bronchiectasis were included in the study. Majority of our patients belonged to severe bronchiectasis group seen in 23 patients (48%) while those with mild and moderate bronchiectasis were seen in 13 (27%) and 12 (25%) patients respectively. The exacerbation rate in mild group was comparable to the predicted BSI exacerbation at 1 year while the predicted and observed rates were statistically significant for moderate and severe bronchiectasis group (p value < 0.05). Mortality rates at 1 year were comparable in all the groups of bronchiectasis while it was comparable only in mild and moderate group bronchiectasis at 4 years. ConclusionBronchiectasis severity index seems to predict mortality at 1 year in post tuberculosis bronchiectasis. However, it under predicts 1 year and 4 year exacerbation rates. Hence BSI may not be useful as a prognostic tool in Indian patients with bronchiectasis. Larger multi-centred studies may be required to further evaluate the clinical utility of BSI among Indian population.

Impulse Oscillometry and Spirometry Small-Airway Parameters in Mild to Moderate Bronchiectasis.

Both impulse oscillometry and spirometry can reflect small-airway disorders. The objective of this work was to investigate the diagnostic value of impulse oscillometry and spirometry small-airway parameters and their correlation with radiology, disease severity, and sputum bacteriology in mild to moderate bronchiectasis (bronchiectasis severity index <9) and to validate these findings in sensitivity analyses (mild bronchiectasis). We recruited 94 subjects with mild to moderate bronchiectasis and 26 healthy subjects. The diagnostic value of small-airway parameters was compared using the receiver operating characteristic curve. Chest high-resolution computed tomography (HRCT), impulse oscillometry measurement, spirometry, and sputum culture were performed. Correlation between small-airway parameters and clinical indices was determined, adjusting for age, sex, body mass index, and smoking history. Sensitivity analyses were repeated when excluding subjects with bronchiectasis severity index ≥9 or HRCT score ≥13. Impulse oscillometry and spirometry small-airway parameters could discriminate mild to moderate bronchiectasis from healthy subjects and correlated significantly with HRCT score and the number of bronchiectatic lobes and the bronchiectasis severity index (all P < .01). Small-airway parameters were more aberrant in subjects with dyshomogeneity and cystic bronchiectasis but were independent of Pseudomonas aeruginosa isolation or the location of predominant bronchiectatic lobes. Spirometry, but not impulse oscillometry, small-airway parameters differed statistically between subjects with isolated peripheral-airway bronchiectasis and those with peripheral plus central-airway bronchiectasis (all P < .01). Subgroup analyses yielded similar findings, except for the lack of correlation between small-airway parameters and clinical parameters in subjects with HRCT score ≤6. Impulse oscillometry and spirometry small-airway parameters have similar diagnostic value in reflecting peripheral-airway disorders and correlate with the HRCT scores, the bronchiectasis severity index, and the number of bronchiectatic lobes in mild to moderate bronchiectasis. Assessment of small-airway parameters should be incorporated in future lung function investigations in bronchiectasis.

Impulse Oscillometry and Spirometry Small Airway Parameters in Mild to Moderate Bronchiectasis

BACKGROUND: Both impulse oscillometry and spirometry can reflect small-airway disorders. The objective of this work was to investigate the diagnostic value of impulse oscillometry and spirometry small-airway parameters and their correlation with radiology, disease severity, and sputum bacteriology in mild to moderate bronchiectasis (bronchiectasis severity index <9) and to validate these findings in sensitivity analyses (mild bronchiectasis). METHODS: We recruited 94 subjects with mild to moderate bronchiectasis and 26 healthy subjects. The diagnostic value of small-airway parameters was compared using the receiver operating characteristic curve. Chest high-resolution computed tomography (HRCT), impulse oscillometry measurement, spirometry, and sputum culture were performed. Correlation between small-airway parameters and clinical indices was determined, adjusting for age, sex, body mass index, and smoking history. Sensitivity analyses were repeated when excluding subjects with bronchiectasis severity index ≥9 or HRCT score ≥13. RESULTS: Impulse oscillometry and spirometry small-airway parameters could discriminate mild to moderate bronchiectasis from healthy subjects and correlated significantly with HRCT score and the number of bronchiectatic lobes and the bronchiectasis severity index (all P < .01). Small-airway parameters were more aberrant in subjects with dyshomogeneity and cystic bronchiectasis but were independent of Pseudomonas aeruginosa isolation or the location of predominant bronchiectatic lobes. Spirometry, but not impulse oscillometry, small-airway parameters differed statistically between subjects with isolated peripheral-airway bronchiectasis and those with peripheral plus central-airway bronchiectasis (all P < .01). Subgroup analyses yielded similar findings, except for the lack of correlation between small-airway parameters and clinical parameters in subjects with HRCT score ≤6. CONCLUSIONS: Impulse oscillometry and spirometry small-airway parameters have similar diagnostic value in reflecting peripheral-airway disorders and correlate with the HRCT scores, the bronchiectasis severity index, and the number of bronchiectatic lobes in mild to moderate bronchiectasis. Assessment of small-airway parameters should be incorporated in future lung function investigations in bronchiectasis.

Validation of a Spanish version of the Leicester Cough Questionnaire in non-cystic fibrosis bronchiectasis.

The Leicester Cough Questionnaire (LCQ) has been validated in non-cystic fibrosis bronchiectasis (NCFBC). The present study aimed to create and validate a Spanish version of the LCQ (LCQ-Sp) in NCFBC. The LCQ-Sp was developed following a standardized protocol. For reliability, we assessed internal consistency and the change in score over a 15-day period in stable state. For responsiveness, we assessed the change in scores between visit 1 and the first exacerbation. For validity, we evaluated convergent validity through correlation with the Saint George's Respiratory Questionnaire (SGRQ) and discriminant validity. Two hundred fifty-nine patients (118 mild bronchiectasis, 90 moderate bronchiectasis and 47 severe bronchiectasis) were included. Internal consistency was high for the total scoring and good for the different domains (Cronbach's α: 0.86-0.91). The test-retest reliability shows an intraclass correlation coefficient of 0.87 for the total score. The mean LCQ-Sp score at visit 1 decreased at the beginning of an exacerbation (15.13 ± 4.06 vs. 12.24 ± 4.64; p < 0.001). The correlation between LCQ-Sp and SGRQ scores was -0.66 (p < 0.01). The differences in the LCQ-Sp total score between the different groups of severity were significant (p < 0.001). The LCQ-Sp discriminates disease severity, is responsive to change when faced with exacerbations and is reliable for use in bronchiectasis.

315 Late diagnosis of CF in a family with R117H

A 60-year-old man with bronchiectasis, nasal polyps, loose stools and a FEV 1 38% predicted was referred for further investigation. He also had bilateral absence of the vas deferens. Extensive bronchiectasis was shown on high resolution CT (HRCT) scanning. Sweat chloride was positive (71.78 mmol/l). Mutation analysis demonstrated F508del and R117H;T[5]. His sputum cultured B. vietnamiensis and S. aureus. Faecal elastase was 114 mg/g. He was established on Dornase alpha and pancreatic enzyme replacement therapy. His FEV 1 improved with an associated reduction in his frequency of exacerbations. Genetic screening of his 6 siblings resulted in 3 of them being diagnosed with CF. They all have F508del and R117H;T[5]. His 57-year-old brother had a history of recurrent chest infections, nasal congestion and infertility. He has moderate bronchiectasis on HRCT and his sputum cultures S. aureus. His 47-year-old sister had a sweat chloride of 89 mmol/l with moderate bronchiectasis on HRCT. She has cultured Mycobacteria avium complex. His 58-year-old brother presented with an FEV1 47% predicted, a sweat chloride of 118 mmol/l and widespread bronchiectasis on HRCT. He has pancreatic insufficiency (faecal elastase S. maltophilia. Discussion It has been suggested that R117H be removed from CF screening panels. R117H may not cause sufficient malfunction of the CFTR protein, however when it is found in cis with a shortened polythymidine sequence, the combination can lead to significantly decreased CFTR function and clinical cystic fibrosis, as demonstrated in this case series. Such individuals may benefit further from CFTR corrector therapy.

Assessment of the Non-Cystic Fibrosis Bronchiectasis Severity: The FACED Score vs the Bronchiectasis Severity Index.

Introduction : Non-cystic fibrosis bronchiectasis (NCFB) is a multidimensional disease, and no single isolated parameter is proved to have sufficient power for any overall determination of its severity and prognosis.Objective : To compare the results of the assessment of the NCFB severity with respect to its prognosis in the same patients by two different validated scores, i.e. the FACED score and the Bronchiectasis Severity Index (BSI).Methods : An observational study including 37 patients with NCFB (16 males and 21 female aged 46 to 76 years) was performed. All patients underwent evaluation of the variables incorporated in the FACED score (FEV1 % predicted, age, chronic colonization by Pseudomaonas aeruginosa, radiological extent of the disease, and dyspnea) and in the BSI (age, body mass index, FEV1 % predicted, hospitalization and exacerbations in previous year, dyspnea, chronic colonization by Pseudomaonas aeruginosa and other microrganisms, and radiological extent of the disease).Results : According to the value of the derived overall FACED score we found 17 patients (45.9%) with mild bronchiectasis, 14 patients (37.8%) with moderate bronchiectasis and 6 patients (16.2%) with severe bronchiectasis. The mean derived FACED score was 3.4 ± 1.3. In addition, according to the value of the derived overall BSI score, the frequency of patients with low, intermediate and high BSI score was 16 patients (43,2%), 14 patients (37.8%) and 7 patients (18.9%), respectively. The mean derived BSI score was 6.4 ± 2.5.Conclusion : We found similar results by the assessment of the NCFB severity in regard to its prognosis by both the FACED score and the BSI. Further studies determining how these scores may impact clinical practice are needed.

Aetiology of bronchiectasis in Guangzhou, southern China.

Aetiologies of bronchiectasis in mainland China and their comparisons with those in western countries are unknown. We aimed to investigate bronchiectasis aetiologies in Guangzhou, southern China, and to determine ethnic or geographic differences with reports from western countries. Consecutive patients with steady-state bronchiectasis were randomly recruited. Past history was meticulously extracted. Patients underwent physical examination, saccharine test, humoral immunity assays, gastroesophageal reflux scoring and sputum culture. Fiberoptic bronchoscopy, total immunoglobin E (IgE) and Aspergillus fumigatus-specific IgE measurement, 24-h gastroesophageal pH monitoring and miscellaneous screening tests were performed, if indicated. This entailed comparisons on aetiologies with literature reports. We enrolled 148 patients (44.6 ± 13.8 years, 92 females), most of whom had mild to moderate bronchiectasis. Idiopathic (46.0%), post-infectious (27.0%) and immunodeficiency (8.8%) were the most common aetiologies. Miscellaneous aetiologies consisted of asthma (5.4%), gastroesophageal reflux (4.1%), aspergillosis (2.7%), congenital lung malformation (2.0%), Kartagener syndrome (1.4%), rheumatoid arthritis (1.4%), chronic obstructive pulmonary disease (0.7%), Young's syndrome (0.7%), yellow nail's syndrome (0.7%), eosinophilic bronchiolitis (0.7%) and foreign bodies (0.7%). No notable differences in clinical characteristics between idiopathic and known aetiologies were found. Ethnic or geographic variations of aetiologies were overall unremarkable. Idiopathic, post-infectious and immunodeficiency constitute major bronchiectasis aetiologies in Guangzhou. Clinical characteristics of patients between known aetiologies and idiopathic bronchiectasis were similar. Ethnicity and geography only account for limited differences in aetiologic spectra. These findings will offer rationales for early diagnosis and management of bronchiectasis in future studies and clinical practice in China.

P125 Heroin Smoking is Associated with Early Onset COPD with Predominant Emphysema

An association between opiate smoking and acute severe asthma is recognised but a relationship with COPD is not clearly established and limited to case reports. Anecdotally there is limited knowledge...

IMAGING DIAGNOSIS: CT FINDINGS IN A DOG WITH INTRACRANIAL HEMORRHAGE SECONDARY TO ANGIOSTRONGYLOSIS

A seven-month-old Cocker Spaniel had a cough, acute lethargy, decreased responsiveness, and episodes of hyperexcitability. There were bilateral generalized increased lung sounds, bilateral episcleral hemorrhage, and systemic hypertension. Prolonged buccal mucosal bleeding time and elevated D-dimer concentrations were detected. Radiographically, there was a generalized moderate unstructured interstitial pattern. In thoracic CT images, there was a diffuse moderate hyperattenuating appearance of the bronchial walls and interstitium and diffuse areas of moderate bronchiectasis. The brain CT images were characterized by marked hyperattenuating well-defined masses. In addition, there were smaller hyperattenuating and hypoattenuating masses scattered throughout the cerebral and cerebellar parenchyma. A zinc sulphate flotation test confirmed large numbers of Angiostrongylus vasorum L1 larvae. Despite therapy the dog continued to deteriorate and underwent euthanasia. Postmortem examination confirmed the presence of multiple intracranial and extracranial hemorrhages. Angiostrongylosis should be considered as one of the differential diagnoses in dogs presenting with neurologic signs consistent with acute intracranial haemorrhage.

Clinical determinants of the 6-Minute Walk Test in bronchiectasis

The 6-Minute Walk Test (6MWT) is a widely used measurement of functional exercise capacity in chronic lung disease. While exercise intolerance has been identified in patients with bronchiectasis, the clinical determinants of the 6MWT in this population have not been examined. The aim of this study was to 1) establish the relationship between the 6-Minute Walk Distance (6MWD), disease severity and Health-Related Quality of Life (HRQOL) and 2) identify predictors of exercise tolerance in adults with bronchiectasis. The 6MWT was performed in 27 patients with bronchiectasis (mean [SD] FEV(1) 73.9% predicted [23.4]). Disease severity was assessed using spirometry and HRCT scoring while HRQOL was evaluated using the St George's Respiratory Questionnaire (SGRQ) and the Short-Form 36 (SF-36). The relationships were evaluated using correlation and multiple regression. The 6MWD correlated positively with FVC (r=0.52, p<0.01), generations of bronchopulmonary divisions (r(s)=0.38, p<0.05) and SF-36 physical summary (r=0.71, p<0.001) while a negative correlation was observed between all domains of the SGRQ (all correlations r>0.5, p<0.001). Multiple regression analysis indicated that the SGRQ activity, symptom scores and generations of bronchial divisions involved were identified as independent predictors of the 6MWD, explaining 76% of the variance. Measures of HRQOL demonstrated a stronger association with the 6MWD compared to physiological measures of disease severity in patients with predominantly mild to moderate bronchiectasis.

Nebulised dornase alpha: adherence in adults with cystic fibrosis

Background: Dornase alpha improves sputum clearance and pulmonary function in patients with moderate bronchiectasis and cystic fibrosis (CF). Several studies have demonstrated variable adherence to treatment regimens in patients with CF. We aimed to compare self-reported adherence with computer based dispensing records of dornase alpha. Method: Direct interview of adherence to dornase alpha was compared with pharmacy-dispensing records during a 12-month period. The reasons for dornase alpha usage, and change in lung function in three groups of patients were compared (group 1 ( n=42): positive trial, continuing therapy; group 2 ( n=13): positive trial, ceased therapy; group 3 ( n=22): negative trial). Ninety patients with CF were surveyed. Patients who had ceased dornase alpha provided reasons for drug cessation. Lung function and anthropometric data were collected prior to dornase alpha treatment and at 3 years. Health care professionals rated adherence to therapy. Results: Of the 42 patients on dornase alpha, the average utilisation was 197 days (54%). From dispensing records, 24% of patients were classified as good adherence, 46% as moderate adherence and 30% as poor adherence. Eighty-two percent claimed to use dornase alpha therapy more than 20 days/month, whereas dispensing records showed that only 24% of collected sufficient drug supplies. Health professionals’ assessment of adherence of therapy was often incorrect and an overestimation was more common than underestimation. The change in FEV 1 3 years after trial was not significantly different between groups. There was a negative correlation between initial response to dornase alpha and baseline FEV 1 ( r=−0.44, P=0.001), however, initial response was not related to the change in FEV 1 over 3 years ( r=0.20, P=0.16). Conclusion: There is variability in adherence to dornase alpha in adults with CF and patient self-reporting is likely to over-estimate drug collection from the pharmacy. Further study of the long-term effects of dornase alpha is required. To date, proven interventions to enhance adherence are limited and require investigation in CF.