Stable Non-cystic Fibrosis Bronchiectasis Research Articles

Primary Immun Deficiency in Patients with Non-Cystic Fibrosis Bronchiectasis and Its Relationship with Clinical Parameters.

Bronchiectasis is characterized by chronic respiratory infection. The role of immunodeficiency in this disease is poorly studied in relation to clinical indices. The primary aim of this study was to determine the frequency of these neglected altered immune status by evaluating immunoglobulins, lymphocyte subsets, complement levels, and neutrophil function, and to assess its relationship with clinical parameters in adult patients with non-cystic fibrosis bronchiectasis (NCFB). A total of 74 (30 men and 44 women with a mean age of 47±17 years) adult patients with stable NCFB were enrolled in this study. The bronchiectasis severity index (BSI) and FACED (F:FEV1, A: Age, C: Chronic colonization, E: Extension, D: Dyspnea) scores were assessed. Peripheral blood samples were collected for the detection of total IgG, IgA, IgM, IgE, and IgG subclasses and C3 and C4 levels. The counts of CD3, CD4, CD8, CD19, CD16/56 expressing peripheral blood lymphocytes and neutrophil oxidative function were evaluated. In the study population, BSI and FACED severity index scores increased with longer duration of the disease (p=0.01 and p=0.040, respectively). Of the 74 patients, 27 (37%) showed humoral aberrations. The number of male patients were higher in this group (p=0.03). High serum total IgE levels were associated with high scores in BSI (moderate-severe group versus mild group, p=0.030). Patients with bronchiectasis demonstrated lower CD3+ T cell count, lower CD4+ T helper cell percentage, and lower CD4+ T cell count (p=0.031, p=0.030, p=0.029, respectively) than healthy subjects. A significant negative correlation was found between the percentage and count of CD16/56+ natural killer (NK) cells and the number of exacerbations within the past year (r=-0.230, p=0.049 and r=-0.264, p=0.023, respectively). Humoral aberrations in adult patients with NCFB were found to be frequent. IgE levels were related to high scores for disease severity indices. Furthermore, patients with low percentage and counts of NK cells had higher rates of exacerbations. These results emphasize the importance of immune function assessment in adult patients with NCFB.

Isolation of and risk factors for airway infection with Pseudomonas aeruginosa in patients with non-cystic fibrosis bronchiectasis.

ABSTRACTObjective:To identify microorganisms in sputum samples of patients with stable non-cystic fibrosis bronchiectasis and to determine risk factors related to the isolation of Pseudomonas aeruginosa (PA) in those patients. Methods:Consecutive patients were recruited from a tertiary hospital outpatient clinic in the city of Fortaleza, Brazil. The patients were submitted to spirometry, six-minute walk test, HRCT, and sputum collection. Data on serum fibrinogen levels, disease severity, sputum color, and history of azithromycin treatment were collected. Results:The study included 112 patients, and females predominated (68%). The mean age was 51.6 ± 17.4 years. Most patients presented with mild-to-moderate disease (83%). The mean six-minute walk distance was 468.8 ± 87.9 m. Mean FEV1 and FVC, in % of predicted values, were 60.4 ± 21.8% and 69.9 ± 18.5%, respectively. The mean serum fibrinogen level was 396.1 ± 76.3 mg/dL. PA was isolated in 47 patients, other potentially pathogenic microorganisms (PPMs) were isolated in 31 patients, and non-PPMs were isolated in 34 patients. Purulent sputum was identified in 77 patients (68%). The patients with PA, when compared with those without it, presented with more severe disease, higher serum fibrinogen levels, and lower FVC%. In addition, purulent sputum and long-term azithromycin treatment were more common in those with PA. The multivariate regression analysis showed that the independent factors associated with PA were serum fibrinogen level > 400 mg/dL (OR = 3.0; 95% CI: 1.1-7.7) and purulent sputum (OR = 4.3; 95% CI: 1.6-11.3). Conclusions:In our sample, the prevalence of PA in sputum was 42%. Sputum color and inflammatory markers were able to predict the isolation of PA, emphasizing the importance of routine sputum monitoring.

Effect of short-term inhalation of warm saline atomised gas on patients with non-cystic fibrosis bronchiectasis.

ObjectiveSecretion clearance is advocated in non-cystic fibrosis bronchiectasis, but is often neglected in clinical treatment. The present study aimed to investigate the effect of inhaled 0.9% normal saline by ultrasonic nebuliser with warming (UNW) in stable non-cystic fibrosis bronchiectasis patients with purulent sputum.Methods27 stable patients were enrolled in a randomised crossover trial comprising 3 months of daily UNW aerosol therapy compared with 3 months of daily oral expectorant treatment. The outcomes were quality of life (assessed via the Leicester cough questionnaire (LCQ)), sputum characteristics, pulmonary function, 6-min walk distance (6MWD) and acute exacerbation frequency.ResultsCompared with baseline, the sputum viscosity, sputum colour, LCQ score and 6MWD were significantly improved with UNW (p<0.05), and the improvements in sputum colour, LCQ score, 6MWD and inspirational capacity with UNW were significantly better than those achieved via treatment with oral expectorant (p<0.05). There were no significant differences between treatments in pulmonary function, sputum cytology classification and inflammatory factors of sputum.ConclusionUNW aerosol therapy in non-cystic fibrosis bronchiectasis has small yet significant benefits. However, UNW does not improve the degree of inflammation.

Inhaled antibiotics therapy for stable non-cystic fibrosis bronchiectasis: a meta-analysis.

Background:The optimum antibiotic therapy for non-cystic fibrosis bronchiectasis (NCFB) has yet to be determined. A meta-analysis was conducted to evaluate the efficacy and safety of inhaled antibiotics in adults with stable NCFB.Methods:PubMed, EMBASE, MEDLINE and the Cochrane Central Register of Controlled Trials were searched through November 2019.Results:A total of 16 randomized controlled trials (RCTs), recruiting 2748 NCFB patients, were finally included. Inhaled antibiotics treatment significantly reduced the sputum bacterial load [standard mean difference (SMD) = –0.74, 95% CI: –1.16–0.32, p < 0.001, I2 = 68.1%], prolonged median time [hazard risk (HR) = 0.73, 95% confidence interval (CI): 0.57–0.93, p < 0.001, I2 = 53.6%] and reduced frequency [incidence rate ratio (IRR) = 0.74, 95% CI 0.63–0.87, p < 0.001, I2 = 20.5%] of exacerbations, with good tolerance. However, it failed to improve Pseudomonas aeruginosa eradication, [forced expiratory volume in 1 s (FEV1)] % predicted, quality of life questionnaire (QoL-B) and St. George’s respiratory questionnaire (SGRQ) scores, and may induce higher risk of P. aeruginosa resistance. Subgroup analysis showed Ciprofloxacin was more effective than other antibiotics in reducing bacterial load (SMD = –1.35, 95% CI: –1.85–0.85, I2 = 63.4%, p = 0.042).Conclusion:Inhaled antibiotics therapy holds great promise for stable NCFB as it is effective in reducing sputum bacterial load and the risk of acute attack, delaying disease progression, and is well tolerated. Although this study brings some constructive ideas in the field of clinical medication, further clinical trials should be carried out, particularly in solving drug-resistance and improving health-related quality of life (HRQoL), which we believe will finally provide benefits for patients suffering from bronchiectasis. The reviews of this paper are available via the supplemental material section.

A Comparison of 2 Respiratory Devices for Sputum Clearance in Adults With Non-Cystic Fibrosis Bronchiectasis.

Airway clearance techniques are a vital part of routine care for patients with bronchiectasis. There is no clear superior modality. The Flutter combines oscillations (6-20 Hz) and positive expiratory pressure; the Lung Flute combines positive expiratory pressure and low frequency acoustic waves (18-22 Hz), to augment clearance. This project aimed to compare these devices. This was a randomized crossover study of adult subjects with stable non-cystic fibrosis bronchiectasis (expectorating > 25 mL/d). Subjects attended 2 separate out-patient visits, 1 week apart, and completed a supervised sputum clearance regime and Lickert scale (8 questions regarding subjects' perception of the experience using each device). Total sputum expectorated during supervised intervention (T1) and after 30 min from the end of T1 (T2) was recorded as wet sputum weight. Total wet sputum weight desiccated in a microwave (10 min at 300 watts), allowed measurement of total dry sputum weight. Data were compared using paired t test. We recruited 40 subjects with a mean ± SD age of 63 ± 16 y. Overall, there was no significant difference in wet sputum weight (Flutter, 5.78 ± 6.47 g; Lung Flute, 5.75 ± 0.22 g) and dry sputum weight (Flutter, 0.40 ± 0.86 g; Lung Flute, 0.22 ± 0.21 g). At T1, wet sputum weight was higher for the Flutter (5.10 ± 6.26 g) compared with the Lung Flute (3.74 ± 3.44 g) (P = .038). At T2, wet sputum weight was higher for the Lung Flute (2.02 ± 3.01 g) compared with the Flutter (0.68 ± 0.75 g) (P = .001). Subjects perceived the Flutter as being significantly better at clearing secretions (P = .01), easy to understand (P = .03), and simple to use (P = .01) compared with the Lung Flute. Both devices were well-tolerated and successfully augmented secretion clearance. Most subjects preferred the Flutter because of increased speed of secretion clearance, and greater ease of use.

Short-Term Effect of Autogenic Drainage on Ventilation Inhomogeneity in Adult Subjects With Stable Non-Cystic Fibrosis Bronchiectasis.

Lung clearance index (LCI), a measure of ventilation inhomogeneity derived from a multiple-breath washout test, is a promising tool for assessing airway function in patients with non-cystic fibrosis bronchiectasis. However, it is unknown whether ventilation inhomogeneity could improve after successful elimination of excessive secretions within bronchiectasis. The objective of this work was to assess the short-term effects of lung secretion clearance using the autogenic drainage technique on standard lung function tests and LCI in subjects with non-cystic fibrosis bronchiectasis. Nitrogen-based multiple-breath washout, spirometry, and body plethysmography tests were performed 30 min before autogenic drainage in adults with stable non-cystic fibrosis bronchiectasis. The autogenic drainage session was followed by a 5-min break, after which the tests were repeated in the same order. Sputum expectorated during autogenic drainage was quantified as dry weight and correlated with change between post- and pre-measurements (Δ). Paired t test or Wilcoxon signed-rank tests were used to compare pre- and post-autogenic drainage measurement outcomes. A P value of ≤.05 was considered as statistically significant. Twenty-four subjects were studied (18 females, median age [range]: 65 [21-81] y). Mean ± SD LCI significantly improved after autogenic drainage (10.88 ± 2.62 vs 10.53 ± 2.35, P = .042). However, only 20% of subjects with mucus hyperproduction during autogenic drainage had a ΔLCI that exceeded measurement variability. The percent of predicted slow vital capacity (SVC%) also slightly improved (88.7 ± 19.3% vs 90 ± 19.1%, P = .02). ΔLCI was inversely related to dry sputum weight (r = -.48, P = .02) and ΔSVC% (r = -.64, P = .001). ΔSVC% also correlated with dry sputum weight (r = 0.46, P = .02). In adults with non-cystic fibrosis bronchiectasis and mucus hypersecretion, autogenic drainage improved ventilation inhomogeneity. LCI change may be the result of the maximum recruited lung volume and the amount of cleared mucus secretion. (ClinicalTrials.gov registration NCT02411981.).

Hiatal hernias are correlated with increased severity of non-cystic fibrosis bronchiectasis.

Hiatal hernias (HH) are associated with gastro-oesophageal reflux and may contribute to lung disease severity. We aimed to evaluate the prevalence of HH among stable non-cystic fibrosis bronchiectasis (NCFB) patients and determine associations with disease severity. A retrospective cross-sectional cohort study of 100 consecutive NCFB patients in our institution was performed. Data were collected on baseline variables, microbiology, lung function and radiology, according to the modified Bhalla score. Disease severity was assessed using the Bronchiectasis Severity Index (BSI) and FACED severity scores. Following expert radiological review, 81 patients were deemed suitable for study inclusion (mean age (SD) 62.6 (12.4), females 55 (67.9%), body mass index (BMI) 26.9 (5.7)); 29 (35.8%) were HH positive (HH+). HH+ patients had a trend towards higher BMI (P = 0.07), and a significantly higher proportion had reflux symptoms (HH+ 62.1% vs HH- 28.8%, P < 0.01). The presence of HH+ was associated with cystic bronchiectasis (HH+ 30.1%, HH- 11.5%; P = 0.03), increased number of lobes involved (HH+ 2.62 (1.54), HH- 2.17 (1.42); P = 0.03), increased extent of bronchiectasis, (HH+ 6.2 (4.7), HH- 4.5 (3.1); P = 0.04), decreased parenchymal attenuation (HH+ 1.0 (1.8), HH- 0.2 (0.5); P = 0.03) and reduced per cent predicted forced expiratory volume in 1 s (HH+ 75.4% (24.5), HH- 90.4% (25.5); P = 0.02). There was no lobar predilection. HH+ was associated with increased disease severity scores: BSI (HH+ 4.93 (1.65), HH- 3.25 (2.13); P < 0.001) and FACED (HH+ 2.21 (1.52), HH- 1.35 (1.43); P < 0.01). HH+ was associated with worse disease severity in NCFB patients, characterized by decreased lung function, increased extent and severity of radiological disease, and increased composite disease severity scores.

Neutrophilic Bronchial Inflammation Correlates with Clinical and Functional Findings in Patients with Noncystic Fibrosis Bronchiectasis.

Background. Neutrophilic bronchial inflammation is a main feature of bronchiectasis, but not much is known about its relationship with other disease features. Aim. To compare airway inflammatory markers with clinical and functional findings in subjects with stable noncystic fibrosis bronchiectasis (NCFB). Methods. 152 NFCB patients (62.6 years; females: 57.2%) underwent clinical and functional cross-sectional evaluation, including microbiologic and inflammatory cell profile in sputum, and exhaled breath condensate malondialdehyde (EBC-MDA). NFCB severity was assessed using BSI and FACED criteria. Results. Sputum neutrophil percentages inversely correlated with FEV1 (P < 0.0001; rho = −0.428), weakly with Leicester Cough Questionnaire score (P = 0.068; rho = −0.58), and directly with duration of the disease (P = 0.004; rho = 0.3) and BSI severity score (P = 0.005; rho = 0.37), but not with FACED. Sputum neutrophilia was higher in colonized subjects, P. aeruginosa colonized subjects showing greater sputum neutrophilia and lower FEV1. Patients with ≥3 exacerbations in the last year showed a significantly greater EBC-MDA than the remaining patients. Conclusions. Sputum neutrophilic inflammation and biomarkers of oxidative stress in EBC can be considered good biomarkers of disease severity in NCFB patients, as confirmed by pulmonary function, disease duration, bacterial colonization, BSI score, and exacerbation rate.

The effects of oscillating positive expiratory pressure therapy in adults with stable non-cystic fibrosis bronchiectasis: A systematic review.

Airway clearance techniques (ACTs) are recommended for patients with stable non-cystic fibrosis (non-CF) bronchiectasis, but the efficacy of oscillating positive expiratory pressure (PEP) therapy compared to other techniques has not been reviewed. A systematic review of studies was conducted in stable patients comparing the effect of oscillating PEP therapy to other ACTs or a control condition. Data were extracted related to sputum expectoration, lung function, gas exchange, quality of life (QOL), symptoms, and exacerbation rate. Seven studies were included with a total of 146 patients, with a mean (SD) PEDro score of 7(1). Oscillating PEP therapy enhanced sputum expectoration compared to no treatment, but has equivalent benefits as the active cycle of breathing technique with gravity-assisted drainage (mean difference [95% CI] -2.8 g [-8.8 to 3.2 g]). Oscillating PEP has a similar effect as other ACTs on dynamic lung volumes, gas exchange and breathlessness. Use of oscillating PEP improved disease-specific QOL (p < 0.001) and cough-related QOL (p < 0.002) compared to no treatment but did not reduce exacerbation rate. In conclusion, in stable non-CF bronchiectasis, oscillating PEP therapy is associated with improvement in sputum expectoration and QOL compared to no treatment. Compared to other ACTs, the effect upon sputum expectoration, lung function, gas exchange, and symptoms are equivalent.

Inhaled antibiotics for stable non-cystic fibrosis bronchiectasis: a systematic review.

We conducted a meta-analysis of randomised trials to evaluate the efficacy and safety of inhaled antibiotics in patients with stable non-cystic fibrosis (CF) bronchiectasis. We searched the Cochrane Airways Group Register of Trials from inception until March 2014. 12 trials with 1264 adult patients were included, of which five were unpublished studies. Eight trials on 590 patients contributed data to the meta-analysis. Amikacin, aztreonam, ciprofloxacin, gentamicin, colistin or tobramycin were used for 4 weeks to 12 months. Inhaled antibiotics were more effective than placebo or symptomatic treatment in reducing sputum bacterial load (five trials; weighted mean difference -2.65 log10 CFU · g(-1), 95% CI -4.38- -0.92 log10 CFU · g(-1)), eradicating the bacteria from sputum (six trials; risk ratio 4.2, 95% CI 1.66-10.64) and reducing the risk of acute exacerbations (five trials; risk ratio 0.72, 95% CI 0.55-0.94). Bronchospasm occurred in 10% of patients treated with inhaled antibiotics compared with 2.3% in the control group (seven trials; risk ratio 2.96, 95% CI 1.30-6.73), but the two groups had the same withdrawal rate due to adverse events (12.2%). Inhaled antibiotics may provide an effective suppressive antibiotic therapy with an acceptable safety profile in adult patients with stable non-CF bronchiectasis and chronic bronchial infection.

Effect of Low-Dose, Long-Term Roxithromycin on Airway Inflammation and Remodeling of Stable Noncystic Fibrosis Bronchiectasis

Background. Noncystic fibrosis bronchiectasis (NCFB) is characterized by airway expansion and recurrent acute exacerbations. Macrolide has been shown to exhibit anti-inflammatory effects in some chronic airway diseases. Objective. To assess the efficacy of roxithromycin on airway inflammation and remodeling in patients with NCFB under steady state. Methods. The study involved an open-label design in 52 eligible Chinese patients with NCFB, who were assigned to control (receiving no treatment) and roxithromycin (receiving 150 mg/day for 6 months) groups. At baseline and 6 months, the inflammatory markers such as interleukin- (IL-)8, neutrophil elastase (NE), matrix metalloproteinase- (MMP)9, hyaluronidase (HA), and type IV collagen in sputum were measured, along with the detection of dilated bronchus by throat computed tomography scan, and assessed the exacerbation. Results. Forty-three patients completed the study. The neutrophil in the sputum was decreased in roxithromycin group compared with control (P < 0.05). IL-8, NE, MMP-9, HA, and type IV collagen in sputum were also decreased in roxithromycin group compared with the control group (all P < 0.01). Airway thickness of dilated bronchus and exacerbation were reduced in roxithromycin group compared with the control (all P < 0.05). Conclusions. Roxithromycin can reduce airway inflammation and airway thickness of dilated bronchus in patients with NCFB.

The role of the high-sensitivity C-reactive protein in patients with stable non-cystic fibrosis bronchiectasis.

Study Objectives. The aim of this study is to investigate the correlation between serum high-sensitivity C-reactive protein (hs-CRP) and other clinical tools including high-resolution computed tomography (HRCT) in patients with stable non-CF bronchiectasis. Design. A within-subject correlational study of a group of patients with stable non-CF bronchiectasis, who were recruited from our outpatient clinic, was done over a two-year period. Measurements. Sixty-nine stable non-CF bronchiectasis patients were evaluated in terms of hs-CRP, 6-minute walk test, pulmonary function tests, and HRCT. Results. Circulating hs-CRP levels were significantly correlated with HRCT scores (n = 69, r = 0.473, P < 0.001) and resting oxygenation saturation (r = −0.269, P = 0.025). HRCT severity scores significantly increased in patients with hs-CRP level of 4.26 mg/L or higher (mean ± SD 28.1 ± 13.1) compared to those with hs-CRP level less than 4.26 mg/L (31.7 ± 9.8, P = 0.004). Oxygenation saturation at rest was lower in those with hs-CRP level of 4.26 mg/L or higher (93.5 ± 4.4%) compared to those with hs-CRP level less than 4.26 mg/L (96.4 ± 1.6%, P = 0.001). Conclusion. There was a good correlation between serum hs-CRP and HRCT scores in the patients with stable non-CF bronchiectasis.

Factors Associated With Lung Function Decline in Adult Patients With Stable Non-Cystic Fibrosis Bronchiectasis

Factors Associated With Lung Function Decline in Adult Patients With Stable Non-Cystic Fibrosis Bronchiectasis

Factors Associated With Lung Function Decline in Adult Patients With Stable Non-Cystic Fibrosis Bronchiectasis

Factors Associated With Lung Function Decline in Adult Patients With Stable Non-Cystic Fibrosis Bronchiectasis

Improvement in health status following bronchopulmonary hygiene physical therapy in patients with bronchiectasis

Chronic productive cough is a common symptom in patients with bronchiectasis that is associated with a reduction in health-related quality of life (QOL). Bronchopulmonary hygiene physical therapy (BHPT) is widely prescribed for patients with bronchiectasis, although the evidence for its efficacy is limited. We set out to prospectively evaluate the impact of BHPT on health-related QOL in patients with non-cystic fibrosis bronchiectasis. We assessed cough symptoms (0-100mm visual analogue scale; VAS) and cough-related QOL in 53 patients with stable non-cystic fibrosis bronchiectasis at baseline and >4 weeks after outpatient-based BHPT. Cough specific health status was assessed with the Leicester Cough Questionnaire (LCQ; total score range 3-21, higher scores representing better QOL). All patients with bronchiectasis complained of cough as the major symptom and had mean (SEM) FEV(1) of 2.1 (0.1)L. Cough-related health status was reduced at baseline; mean (SEM) LCQ score 14.3 (0.6). There were significant improvements in cough symptoms (mean cough VAS before 43.3 (3.6) vs after 27.5 (3.1); mean difference 15.8; 95% CI of difference 9.6-22; p<0.0001) and cough-related health status after BHPT (mean LCQ total score before 14.2 vs after 17.3; mean difference 3.1; 95% confidence interval of difference 2.4-3.9; p<0.001). A significant improvement was seen in all LCQ health-related domains (physical, psychological and social; all p<0.001). Our findings suggest that bronchopulmonary hygiene physical therapy can lead to a significant improvement in cough-related quality of life.

Factors Associated With Lung Function Decline in Adult Patients With Stable Non-Cystic Fibrosis Bronchiectasis

Bronchiectasis remains a major public health problem, but factors influencing its natural history are not well characterized. The objective of our study was to explore modifiable and nonmodifiable factors associated with lung function decline in a clinical cohort of patients with stable non-cystic fibrosis (CF) bronchiectasis. Seventy-six stable adult patients (mean age, 69.9 years; 48.7% men) with bronchiectasis were included. The diagnosis of bronchiectasis was established in all cases by high-resolution CT scanning. Baseline data were collected on clinical history, symptoms, disease extension, treatment, sputum volume, microbiological aspects, laboratory findings, and exacerbations. All patients were invited to attend the clinic every 6 months for 24 months to conduct full spirometry and microbiological analysis of sputum, and to report the number of exacerbations. Overall, the group experienced a rate of decline of lung function (FEV1) of 52.7 mL per year. Independent factors associated with an accelerated decline of lung function were chronic colonization with Pseudomonas aeruginosa (PA) [odds ratio (OR), 30.4; 95% confidence interval (CI), 3.8 to 39.4; p=0.005], more frequent severe exacerbations (OR, 6.9; 95% CI, 2.3 to 10.5; p=0.014), and more systemic inflammation (OR, 3.1; 95% CI, 1.9 to 8.9; p=0.023). Regrettably, none of the long-term treatment strategies evaluated, including the use of long-acting inhaled bronchodilators, inhaled or oral steroids, oxygen therapy, secretion clearance maneuvers, or antibiotics had a significant effect on FEV1 decline. Chronic colonization by PA, severe exacerbations, and systemic inflammation are associated with disease progression in non-CF bronchiectasis.