Quality of life and inflammation in exacerbations of bronchiectasis

Patients with bronchiectasis often have impaired quality of life (QoL), which deteriorates with exacerbations. The aim of this study was to investigate changes in QoL and how these were influenced by changes in airway physiology and inflammation in patients with bronchiectasis before and after resolution of an exacerbation. Sputum induction and a QoL questionnaire were undertaken on the first day, day 14, and 4 weeks after completion of intravenous antibiotics (day 42). Eighteen patients (12 female) were recruited, median (IQ range) age of 54 (47-60) years. There was a trend towards an improvement in lung function from visit 1 to visit 2, but this was not statistically significant. C-reactive protein (CRP) [mean (SEM)] reduced between visit 1 and visit 2 [55.4 (21.5) vs 9.4 (3.1) mg/L, P = 0.03] but did not increase significantly on visit 3 [44.4 (32.9) mg/L, P = 0.27]. The median (interquartile range) sputum cell count (x10(6) cells/g of sputum) decreased from visit 1 to visit 2 [21.6 (11.8-37.6)-13.3 (6.7-22.9) x 10(6) cells/g, respectively, P = 0.008] and increased from visit 2 to visit 3 [26.3 (14.1-33.6) x 10(6) cells/g, P = 0.03]. All soluble markers of inflammation significantly reduced from visit 1 to visit 2 but increased on visit 3 with the exception of TNF-alpha. Regarding QoL, three of the four domains (dyspnoea, emotional, mastery) significantly improved from visit 1 to visit 2 but did not change between visit 2 and visit 3. The improvements in QoL scores could not be explained by the improvements in lung function or inflammatory markers.     

Inhaled mannitol in the treatment of non-cystic fibrosis bronchiectasis in adults

Bronchiectasis is a chronic disorder characterized by impaired mucociliary clearance and a relentless cycle of infection, inflammation and bronchial wall injury, which has a debilitating impact on the patient's quality of life and results in increased morbidity and mortality. It is a disease for which there are no currently registered therapeutic products, limited epidemiological data and no validated endpoints that have been accepted by the majority of regulatory authorities. This article reviews the evidence base for the efficacy of inhaled dry powder mannitol in patients with non-cystic fibrosis (CF) bronchiectasis. The few published papers on this topic concluded that mannitol, when inhaled as a dry powder, is a promising treatment for bronchiectasis. It is designed to hydrate the lungs and restore normal mucociliary clearance mechanisms in the lungs. Based on the available evidence, mannitol inhalation is well tolerated and improves the quality of life of patients with non-CF bronchiectasis. There is a need for well designed and adequately powered multicentre trials to establish the potential usefulness of mannitol as a treatment for non-CF bronchiectasis.     

Body mass index and response to emergency department treatment in adults with severe asthma exacerbations: a prospective cohort study

BACKGROUND: In acute asthma (AA), overweight/obesity (body mass index [BMI]>or=25 kg/m2) have been related to poorer outcomes and higher risk of complications. METHODS: We designed a prospective cohort study to determine if overweight/obese adults with severe episodes of AA require longer duration of emergency department (ED) treatment and have higher hospitalization rates compared with underweight/normal asthmatics (BMI<25 kg/m2). All patients received inhaled albuterol (maximum 6 h). Patients were discharged or admitted according to standard accepted criteria. The weight and height of each patient were measured during the ED stay. RESULTS: Four hundred twenty-six patients (mean, 33.4+/-11.5 years [+/-SD]; 63% women) with severe exacerbations (FEV1, 28.2+/-11.9% of predicted) were enrolled. One hundred sixty-three patients (38.3%) were classified as overweight/obese. Patients with BMI>or=25 kg/m2 showed significant increases in length of ED stay (2.3 h vs 1.9 h, p=0.01) and rate of hospitalization (13.7% vs 6.8%, p=0.02), despite adjustments for other confounding variables. They also presented a higher rate of use of inhaled steroids and theophylline within the past 7 days. At the end of treatment, overweight/obese patients displayed more wheezing. Multivariate analysis demonstrated that BMI>or=25 kg/m2 resulted unrelated to final change in peak expiratory flow from baseline. By contrast, BMI>or=25 kg/m2 was related with duration of ED treatment (p=0.002). CONCLUSIONS: Overweight/obese patients were admitted to the hospital more frequently than underweight/normal patients. This may reflect a difference in the perception of dyspnea, or it may reflect an underlying difference in asthma severity between the two groups.     

Ofloxacin compared with amoxycillin in treating infective exacerbations in bronchiectasis

Forty-one hospitalized adult patients of bronchiectasis (non-cystic fibrotic) with infective exacerbations were entered into a randomized, double-blind, placebo-controlled study comparing ofloxacin (200 mg tid) and amoxycillin (1 g tid) both orally for ten days. In the ofloxacin group (20 patients), improvement in sputum purulence was excellent in 14, and fair in five patients with one failure. In the amoxycillin group (21 patients), improvement in sputum purulence was excellent in eight, fair in five and poor in eight patients. Mean drug levels on day 5 were 4.1 mg l-1 for serum (2 h post-dosage) and 4.0 mg l-1 for sputum for ofloxacin, and 18.4 mg l-1 for serum and 0.3 mg l-1 for sputum for amoxycillin. Ofloxacin thus yielded higher sputum concentration and appeared to be more effective and also better tolerated than amoxycillin in infective episodes of bronchiectasis.     

Susceptibility to exacerbations in Black adults with asthma

Objective: Exacerbations account for much of the morbidity in asthma. In a large intervention study, we sought to test the hypothesis that a Black adult exacerbation-prone phenotype – a group of Black people with asthma who are at high risk of repeat exacerbation within one year – exists in asthma independent of clinical control. Methods: We analyzed exacerbation risk factors in 536 self-identified Black Americans with asthma eligible for, or on, Step 3 National Asthma Education and Prevention Program (NAEPP) therapy who participated in a randomized 6–18?month trial of tiotropium versus long acting beta agonist as add-on therapy to inhaled corticosteroids. Exacerbations were defined as events treated by oral or systemic corticosteroids. Clinical control was assessed by a validated asthma control questionnaire (ACQ5). Results: Exacerbations became more likely with loss of clinical control. The mean baseline ACQs for exacerbators and non-exacerbators were 2.41 and 1.91, respectively (p?<?0.001). The strongest independent factor associated with exacerbations across all ACQ levels was an exacerbation in the preceding year (adjusted OR 3.26; p?<?0.001). The severity of prior exacerbations did not correlate with the likelihood of a future exacerbation. Lower baseline FEV1/FVC was also associated with increased risk of exacerbations. Conclusions: Even though exacerbations increase with loss of clinical control, an exacerbation susceptibility phenotype exists in Black adults with asthma, independent of clinical control. This phenotype requires precision therapeutic targeting.     

肺康复运动用于支气管扩张急性加重患者恢复期的效果评价

目的评估肺康复运动用于支气管扩张急性加重患者恢复期的治疗效果。方法纳入支气管扩张患者共计60例。患者于支气管扩张急性发作时入院使用抗菌药物治疗14天后,依据随机数字表将患者随机分配至肺康复运动组(pulmonary rehabilitation group,P组)或标准治疗组(control group,C组)。C组患者进行宣传教育;P组患者在C组基础上进行为期4周的肺康复运动。于支气管扩张急性发作时(T0)、抗菌药物治疗结束(T2)、肺康复运动结束(T6)、肺康复运动结束后4周(T10)评估患者6 min步行试验(6 minutes walk test,6MWT)结果。使用圣乔治呼吸问卷(St.George Respiratory Questionnaire,SGRQ)评估上述时点患者生活质量。结果P组患者T6时点6MWT明显高于T2时点,而SGRQ评分显著低于T2时点,差异有统计学意义(P<0.05)。P组患者T6时点6MWT显著高于C组患者,但SGRQ评分低于C组患者,差异有统计学意义(P<0.05)。结论为期4周的肺康复运动能够有效提升支气管扩张急性加重后患者的运动耐力、改善患者生活质量,但该效果无法长期持续。     

Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas aeruginosa infection in adult bronchiectasis

RATIONALE: Pseudomonas aeruginosa lung infection in patients with bronchiectasis, a chronic airway disease that is characterized by episodes of exacerbation, is associated with more severe disease and a higher utilization of health-care resources. Inhaled tobramycin solution reduces the number of acute exacerbations in patients with cystic fibrosis (CF)-related bronchiectasis with P aeruginosa infection but remains untested in the treatment of exacerbations in patients with non-CF bronchiectasis. OBJECTIVES: This study tested the effect of adding inhaled tobramycin solution to oral ciprofloxacin (Cip) for the treatment of acute exacerbations of non-CF bronchiectasis in patients with P aeruginosa infection. METHODS: A double-blind, randomized, active comparator, parallel-design study conducted at 17 study centers (5 in the United Kingdom, and 12 in the United States) compared 2 weeks of therapy with Cip with either an inhaled tobramycin solution or placebo in 53 adults with known P aeruginosa infection who were having acute exacerbations of bronchiectasis. MEASUREMENTS: Clinical symptoms, pulmonary function, clinical efficacy, and sputum microbiology were investigated prospectively. Main results: An inhaled solution of Cip with tobramycin, compared to placebo, achieved greater microbiological response but no statistically significant difference in clinical efficacy at days 14 or 21. Clinical and microbiological outcomes at the test of cure (ie, the clinical outcome assessment at day 21) were concordant when an inhaled tobramycin solution was added to therapy with Cip and compared to placebo (p = 0.01). Both subject groups had similar overall adverse event rates, but subjects receiving therapy with an inhaled tobramycin solution reported an increased frequency of wheeze (50%; placebo group, 15%). CONCLUSIONS: The addition of an inhaled tobramycin solution to therapy with oral Cip for the treatment of acute exacerbations of bronchiectasis due to P aeruginosa improved microbiological outcome and was concordant with clinical outcome; the inability to demonstrate an additional clinical benefit may have been due to emergent wheeze resulting from treatment.     

Bronchodilator response in adults with bronchiectasis: correlation with clinical parameters and prognostic implications

Background

Bronchial dilation testing is an important tool to assess airway reversibility in adults with bronchiectasis. This study aims to investigate the association of bronchodilator response (BDR) and clinical parameters in bronchiectasis, and the utility of BDR to indicate lung function decline and risks of bronchiectasis exacerbations (BEs).

Methods

We recruited 129 patients with clinically stable bronchiectasis. Baseline measurements included assessment of sputum inflammation and matrix metalloproteinase-8 and -9, sputum bacterial culture, spirometry, bronchial dilation test (for baseline FEV₁ less than 80% predicted only) and chest high-resolution computed tomography (HRCT). Bronchiectasis patients were followed-up for 1 year to determine the incidence of BEs and lung function trajectories. Significant BDR was defined as FEV₁ improvement from pre-dose value by at least 200 mL and 12%. Clinical trial registry No.: {"type":"clinical-trial","attrs":{"text":"NCT01761214","term_id":"NCT01761214"}}NCT01761214; URL: www.clinicaltrials.gov.

Results

BDR was negatively correlated with baseline FEV₁ percentage predicted, but not blood or sputum eosinophil count. Significant BDR was not associated with greater proportion of never-smokers, poorer past history, greater HRCT scores, poorer diffusing capacity or increased sputum matrix metalloproteinases (all P>0.05). There was a trend towards higher bronchiectasis severity index (BSI) and greater proportion of patients with Pseudomonas aeruginosa isolation or infection. Significant BDR at baseline was linked to poorer spirometry, but not more rapid lung function decline, throughout follow-up. Patients with significant BDR demonstrated non-significantly lower risks of experiencing the first BEs than those without (P=0.09 for log-rank test).

Conclusions

Significant BDR is associated with poorer lung function compared with non-significant BDR. Whether BDR predicts future risks of BEs needs to be tested in a larger cohort.     

Socioeconomic deprivation, readmissions, mortality and acute exacerbations of bronchiectasis

Background: Bronchiectasis is known to cause significant morbidity in children in New Zealand. Little is known of the disease in adults. Aim: Our objective was to characterise a cohort of adults who presented to hospital with acute exacerbations of the disease. Methods: We retrospectively collected information on all exacerbations treated as inpatients from a single hospital in South Auckland, New Zealand during 2002. Results: We collected information on 307 exacerbations in 152 patients. Twenty‐seven per cent were of Maaori ethnic origin, and 44% Pacific. Seventy per cent lived in areas categorised as the 20% most deprived in New Zealand. Comorbid conditions were present in 80% of patients – most commonly chronic obstructive pulmonary disease, asthma, diabetes and cardiac disease. Seventy (46%) patients had at least one readmission and 32 patients (21%) died within 12 months of admission to hospital. Greater deprivation was associated with increased mortality at 12 months after admission after adjusting for other factors (OR 11, 95% CI 2.0–61, P= 0.006). In the subgroup who underwent high‐resolution computed tomographic scanning (93), increasing severity of bronchiectasis (modified Bhalla score) was associated with readmission within 12 months (P= 0.004), but not mortality (P= 0.419). Conclusions: We have shown that exacerbations of bronchiectasis in South Auckland are more common in patients who are predominantly of Maaori or Pacific descent and are socioeconomically deprived. Admission to hospital for an exacerbation is associated with high readmission and mortality rates.     

The initial evaluation of adults with bronchiectasis

Bronchiectasis can be caused by a myriad of underlying conditions or environmental insults to the bronchial tree. Despite a detailed evaluation, the cause remains undetermined in approximately 50% of cases. Nonetheless, it is important to use a systematic approach to the diagnostic evaluation of a patient with newly diagnosed bronchiectasis, because a substantial proportion of patients have a specific underlying diagnosis with implications for prognosis or treatment. There is not one panel of tests that can be recommended for all patients. This article reviews the initial evaluation of an adult patient with bronchiectasis.     

Exhaled breath condensate pH and ammonia in cystic fibrosis and response to treatment of acute pulmonary exacerbations

Exhaled breath condensate (EBC) pH reflects the acid–base homeostasis of the airway lining fluid and is up to 3 log order lower in various inflammatory lung diseases including asthma, COPD, bronchiectasis, and cystic fibrosis (CF) than in normal controls. The aim of this study was to confirm this finding in CF and determine if there was a significant change in EBC pH after treatment of an acute pulmonary exacerbation. Ten subjects with CF and a pulmonary exacerbation, and 10 healthy age‐matched control subjects were studied. EBC was collected at the onset of an acute pulmonary exacerbation and after treatment with intravenous antibiotics (median duration: 14 days (interquartile range, IQR): 12–14) when the exacerbation was considered resolved. The median age for CF patients was 15.9 years (IQR: 13–18.8), compared to 18 years (IQR: 15–24.8) for the control group, P = 0.242. All CF subjects had severe lung disease, median FEV₁ = 41.5% of predicted (IQR: 30.8–46.5%). Median EBC pH in CF subjects at the onset of a pulmonary exacerbation was 6.61 (IQR: 6.17–7.91) compared to median EBC pH of 8.14 (IQR: 7.45–9.08) in the control group, P < 0.02. Median EBC pH after resolution of an exacerbation was 7.02 (IQR: 5.8–8.64), not significantly different (P = 0.667) than during the acute exacerbation. EBC pH decreased in five subjects, increased in three subjects and there was no change in two subjects. There was no correlation between EBC pH and FEV₁ either before or after intravenous antibiotics. EBC ammonia, an important buffer of ASL, was also measured and similarly found to be lower than in normal controls. EBC pH is lower in CF than age‐matched controls, and did not change consistently in response to treatment of an acute pulmonary exacerbation. Pediatr Pulmonol. 2009; 44:866–872. © 2009 Wiley‐Liss, Inc.     

Role of bromhexine in exacerbations of bronchiectasis. Double-blind randomized multicenter study versus placebo.

The effectiveness of bromhexine in the treatment of patients with bronchiectasis, in a stage of clinical exacerbation, was assessed in a double-blind, placebo-controlled trial involving 88 in-patients. Bronchiectasis was diagnosed by bronchography and/or CT scan. Bromhexine or matched placebo was administered as 30-mg capsules three times daily per os. Ceftazidine, 1 g i.m., was given to all patients once a day for the first week only. Bromhexine seemed to improve the clinical picture, with significantly positive trends for expectoration, quantity of sputum and auscultatory findings. It also increased the FEV1 and was well-tolerated. Both patients and investigators judged it efficacious.     

Relationship between exhaled nitric oxide and treatment response in COPD patients with exacerbations

Background and objective: Fractional exhaled nitric oxide (FENO) has been implicated as a pulmonary biomarker in various respiratory diseases, including COPD. In this longitudinal study, the benefit of measuring FENO in a routine clinical setting was assessed in COPD patients hospitalized with an exacerbation of the disease. Methods: FENO, lung function and blood gases were measured in 58 COPD patients at hospital admission due to an exacerbation, and at discharge following treatment with corticosteroids and bronchodilators. Results: FENO levels were significantly decreased at discharge, compared with those at admission (geometric mean 25.3 ppb (95% CI: 21.2–30.1) vs 19.7 ppb (95% CI: 17.2–22.6); P = 0.002). There was a significant positive correlation between FENO concentrations at admission and the increase in FEV₁ after treatment (r = 0.441, P < 0.001), and a significant inverse correlation between FENO values at admission and the mean length of hospital stay (r = ?0.297, P = 0.016). Using receiver operating characteristic curve analysis, the optimum cut point for FENO as a predictor for significant increase in FEV₁ was 26.8 ppb (sensitivity: 74%, specificity: 75%). There were no correlations between FENO levels and absolute values for lung function variables at admission or discharge. Conclusions: These data suggest that FENO levels determined at hospital admission may predict the overall response to treatment in COPD patients with acute exacerbations.     

Aetiology of bronchiectasis in adults: A systematic literature review

While identifying the underlying aetiology is a key part of bronchiectasis management, the prevalence and impact of identifying the aetiologies on clinical management remain unclear. We aimed to determine the etiological spectrum of bronchiectasis, and how often etiological assessment could lead to the changes in patients' management. A comprehensive search was conducted using MEDLINE (via PubMed) and EMBASE for observational studies published before October 2015 reporting aetiologies in adults with bronchiectasis. Of the 8216 citations identified, 56 studies including 8608 adults with bronchiectasis were relevant for this systematic review. The crude prevalence for the identified aetiologies ranged from 18% to 95%, which possibly resulted from the differences in the geographic regions and diagnostic workup. Post‐infective (29.9%), immunodeficiency (5%), chronic obstructive pulmonary disease (3.9%), connective tissue disease (3.8%), ciliary dysfunction (2.5%), allergic bronchopulmonary aspergillosis (2.6%) were the most common aetiologies. In 1577 patients (18.3%), identifying the aetiologies led to changes in patient's management. Aetiologies varied considerably among different geographic regions (P < 0.001). Intensive investigations of these aetiologies might help change patient's management and therefore should be incorporated into routine clinical practice.     

支气管扩张症发病机制及治疗进展

支气管扩张症在世界范围内发病率均有所增加,但其异质性较强,目前对其病因、发病机制及有效治疗等方面的研究相对较少,我们对这一疾病还有待进一步认识.目前认为其发病机制主要有免疫失调及细菌定植两个方面.近来大环内酯类抗生素对支气管扩张症的治疗方面也取得了一些进展.本文就非囊性纤维化支气管扩张症流行病学、病因学、发病机制及治疗方面的进展进行综述.