Disease Severity In Bronchiectasis Research Articles

The prevalence of anxiety and depression in bronchiectasis patients and their association with disease severity: a cross-sectional study

Bronchiectasis is a chronic lung disease characterized by recurrent respiratory symptoms. Several studies demonstrated that psychological comorbidities are common in patients with bronchiectasis. The aim of this study is to investigate the prevalence of anxiety and depression in bronchiectasis patients and assess their association with disease severity. In this cross-sectional study, we included patients diagnosed with bronchiectasis. The study was conducted using an interviewer-administered questionnaire via phone calls and data collected from the electronic medical records at JUH. The questionnaire included patients’ demographics and disease characteristics. Anxiety and depression were assessed using GAD7 and PHQ9 respectively. Bronchiectasis disease severity was assessed using BSI and FACED score. The total number of included patients was 133. Moreover, 53.4% of the participants were females while the rest were males (46.6%). PHQ9 demonstrated that 65.4% of the patients had depression. Regarding anxiety, GAD7 scale showed that 54.1% of the patients had anxiety. Pearson correlation showed that bronchiectasis severity index was significantly associated only with PHQ9 depression scores (r = 0.212, P value = 0.014). The prevalence of depression and anxiety is high among patients with bronchiectasis. We believe that patients affected with bronchiectasis should be screened for depression to improve their quality of life.

The Predictive Role of Psychological Status and Disease Severity Indexes on Quality of Life Among Patients with Non-CF Bronchiectasis.

Bronchiectasis is a chronic suppurative lung disease that significantly impacts the patients' quality of life. Aim of this study is to evaluate the relationship between life of quality and patient's psychological status and bronchiectasis disease severity indexes in patients with non-Cystic Fibrosis (CF) bronchiectasis. We also aimed to investigate the validity and reliability of Turkish version of Quality-of-Life Questionnaire-Bronchiectasis (QoL-B V3.1) in Turkish adult bronchiectatic patients. 90 stable non-CF bronchiectatic adult patients were enrolled into this study. At baseline, dyspnea score, BMI, lung function tests, sputum cultures, number of exacerbations and hospital admissions, disease severity indexes were recorded. All of the participants underwent quality of life assessment using both QoL-B V3.1 and of Short-Form (SF)-36 questionnaires, psychological status was evaluated by using HADS (Hospital Anxiety and Depression Scale). In all study participants, anxiety was diagnosed in 27/90 (30%) of patients and depression was diagnosed in 37/90 (41%) of patients. Patients with anxiety and depression had lower quality of life scores in various domains (p:0.026-p:0.001) and HADS scores negatively correlated with several quality-of-life domains (r=-0.216 - r=- 0.343). Female patients had higher risk for depression (55% vs 22%, p:0.002) and worse quality of life than males (p:0.016-p:0.038). Several life quality scores of both instruments were worse in patients with moderate-severe disease severity indexes when compared with those of mild groups. Moreover, Turkish version of newly described QoL-B V3.1 questionnaire was found to be reliable and valid instrument to evaluate the quality of life. These results emphasize the importance of mental health and disease severity as significant determinants of the life quality in patients particularly female patients with non-CF bronchiectasis.

The Predictive Role of Psychological Status and Disease Severity Indexes on Quality of Life Among Patients with Non-CF Bronchiectasis

Objective Bronchiectasis is a chronic suppurative lung disease that significantly impacts the patients’ quality of life. The aim of this study is to evaluate the relationship between quality of life and patient’s psychological status and bronchiectasis disease severity indexes in patients with non-cystic fibrosis bronchiectasis. We also aimed to investigate the validity and reliability of Turkish version of Quality of Life Questionnaire-Bronchiectasis (V3.1) in Turkish adult bronchiectatic patients.MATERIAL AND Methods In total, 90 stable non-cystic fibrosis bronchiectatic adult patients were enrolled in this study. At baseline, dyspnea score, body mass index, lung function tests, sputum cultures, number of exacerbations and hospital admissions, and disease severity indexes were recorded. All of the participants underwent quality of life assessment using both Quality of Life Questionnaire-Bronchiectasis V3.1 and Short Form-36 questionnaires, and psychological status was evaluated by using Hospital Anxiety and Depression Scale.Results In all study participants, anxiety was diagnosed in 27/90 (30%) of patients, and depression was diagnosed in 37/90 (41%) of patients. Patients with anxiety and depression had lower quality of life scores in various domains (P = .026-.001), and Hospital Anxiety and Depression Scale scores negatively correlated with several quality of life domains (r = −0.216 to 0.343). Female patients had higher risk for depression (55% vs 22%, P = .002) and worse quality of life than males (P = .016-.038). Several life quality scores of both instruments were worse in patients with moderate–severe disease severity indexes when compared with those of mild groups. Moreover, Turkish version of newly described Quality of Life Questionnaire-Bronchiectasis V3.1 questionnaire was found to be a reliable and valid instrument to evaluate the quality of life.Conclusion These results emphasize the importance of mental health and disease severity as significant determinants of the life quality in patients, particularly female patients with non-cystic fibrosis bronchiectasis.

Sputum Neutrophil Elastase in pediatric cystic fibrosis and non-cystic fibrosis bronchiectasis

Abstract Objective To assess the value of sputum neutrophil elastase as a biomarker of severity in cases of non-cystic fibrosis bronchectasis & cystic fibrosis. Methods This cross-sectional study was conducted on 50 bronchiectasis patients aged from 1 to 13 years presented to pediatric chest clinic and department of Ain shams university hospital., there were classified into 2 groups; Group A cystic fibrosis patients(30) and group B non-cystic fibrosis bronchiectasis patients(20). Inclusion criteria :children aged from 1 to 16 years, patients were diagnosed with bronchiectasis clinically and with HRCT chest and cystic Fibrosis patients were diagnosed by positive sweat chloride test and genetic study. Exclusion Criteria includes no other known chronic lung diseases. All patients were evaluated by full medical history and full clinical examination, the following lab investigations were done :sweat chloride test, CFTR mutation study, sputum sampling and culture. Quantitative sputum neutrophil elastase assay was done, and the severity of disease was assessed using clinical scores as SK score ,FACED score and bronchiectasis severity index and by using radiological scores as Bhalla and modified Reiff score. Results Steatorrhea was more prevalent among cystic fibrosis patients (80%) than non-CF bronchiectasis patients (0%).(P = 0.00). Clubbing was more prevalent among non -cystic fibrosis bronchectasis (10) (50 %), than cystic fibrosis (2 patients) (6.7 %).(P = 0.00). In cystic fibrosis, neutrophil elastase was significantly higher among severe group (126 ng/mL) than among the moderate (30 ng/mL) and mild (16 ng/mL) groups.(P = 0.00). While in non-CF bronchiectasis patients, neutrophil elastase was significantly higher among severe group (67 ng/mL) than among the moderate (24 ng/mL) and mild (11 ng/mL) groups.(P = 0.00) Conclusion There was a significant correlation between sputum neutrophil elastase and disease severity in bronchiectasis (both cystic fibrosis and non-CF).

Neutrophil dysfunction in bronchiectasis: an emerging role for immunometabolism.

Bronchiectasis is a heterogenous disease with multiple underlying causes. The pathophysiology is poorly understood but neutrophilic inflammation and dysfunctional killing of pathogens is believed to be key. There are, however, no licensed therapies for bronchiectasis that directly target neutrophilic inflammation. In this review, we discuss our current understanding of neutrophil dysfunction and therapeutic targeting in bronchiectasis. Immunometabolic reprogramming, a process through which inflammation changes inflammatory cell behaviour by altering intracellular metabolic pathways, is increasingly recognised across multiple inflammatory and autoimmune diseases. Here, we show evidence that much of the neutrophil dysfunction observed in bronchiectasis is consistent with immunometabolic reprogramming. Previous attempts at developing therapies targeting neutrophils have focused on reducing neutrophil numbers, resulting in increased frequency of infections. New approaches are needed and we propose that targeting metabolism could theoretically reverse neutrophil dysfunction and dysregulated inflammation. As an exemplar, 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation has already been shown to reverse phagocytic dysfunction and neutrophil extracellular trap (NET) formation in models of pulmonary disease. AMPK modulates multiple metabolic pathways, including glycolysis which is critical for energy generation in neutrophils. AMPK activators can reverse metabolic reprogramming and are already in clinical use and/or development. We propose the need for a new immunomodulatory approach, rather than an anti-inflammatory approach, to enhance bacterial clearance and reduce bronchiectasis disease severity.

The detrimental qualitative and quantitative alterations of circulating endothelial progenitor cells in patients with bronchiectasis

BackgroundBronchiectasis is an independent risk factor for cardiovascular disease（CVD）and cardiac dysfunction. Endothelial progenitor cells (EPCs) play a crucial role in maintaining endothelial function, and is inversely correlated with cardiovascular risk factors or cardiac dysfunction. However, the relationship between EPCs and bronchiectasis is unknown. MethodsTwenty-nine patients with stable bronchiectasis and 15 healthy controls were recruited. Fasting venous blood were collected for determining circulating EPC number and activity as well as systemic inflammatory cytokines. ResultsThe number and migratory or proliferative activity of circulating EPCs in bronchiectasis patients were significantly reduced (p < 0.001). In high E-FACED group, the number of circulating EPCs evaluated by cell culture assay and EPC proliferation were decreased (p < 0.05). Similarly, the number and function of circulating EPCs were both reduced in low forced expiratory volume in 1 s (FEV1) or high mMRC group (p < 0.05). There was a significant correlation between circulating EPCs and bronchiectasis disease severity, according to the E-FACED score (p < 0.05), particularly to FEV1 (p < 0.05) and mMRC dyspnea score (p < 0.05). The count and activity of EPCs inversely correlated with hsCRP levels and IL-6 levels (p < 0.01). ConclusionsDeficiencies in the number and function of circulating EPCs are present in patients with bronchiectasis. The changes are related to disease severity and may be partly attributed to systemic inflammation. The current findings may provide novel surrogate evaluation biomarkers and potential therapeutic target for bronchiectasis.

Evaluation of disease severity in bronchiectasis using impulse oscillometry.

Although the diagnostic value of impulse oscillometry (IOS) in bronchiectasis for the differential diagnosis of healthy subjects has been researched, the usefulness of each IOS parameter for predicting disease severity in bronchiectasis has not been thoroughly investigated. In addition, the usefulness of IOS in patients with nontuberculous mycobacteria (NTM) infection has not been reported. This study aimed to determine the predictive significance of respiratory impedance and detect the other most significant IOS parameters for predicting disease severity in bronchiectasis patients and to validate the usefulness of IOS in patients with NTM infection.A total of 206 patients with bronchiectasis who attended clinics at the National Hospital Organization Osaka Toneyama Medical Center were included. Chest high-resolution computed tomography, spirometry and IOS were performed. Hospital admissions, mortality and disease severity indices for bronchiectasis (Bronchiectasis Severity Index (BSI), FACED, and E-FACED scores) were calculated to assess disease severity. The patients were divided into subgroups with and without NTM infection, and subgroup analyses were performed.Respiratory reactance, especially resonant frequency (fres), correlated with both BSI and FACED score better than respiratory resistance. Inspiratory but not expiratory impedance was strongly correlated with BSI, FACED and E-FACED scores. Inspiratory fres was the most useful predictor, increasing as the disease became more severe. The usefulness of IOS was almost equivalent in patients both with and without NTM infection.Inspiratory reactance measured by IOS is useful for estimating disease severity in bronchiectasis. Inspiratory fres best predicts disease severity in bronchiectasis patients both with and without NTM infection.

Clinical impact of depression and anxiety in patients with non-cystic fibrosis bronchiectasis.

Bronchiectasis is a chronic suppurative disease characterized by abnormal bronchial dilatation. The nature of bronchiectasis may have negative impact on psychological status, however it is poorly studied in relation to clinical indices, particularly the severity of disease. Primary aim of this study is to detect depression and anxiety in patients with non-cystic fibrosis bronchiectasis and to evaluate its relationship with disease severity indexes. Ninety (male/female= 37/53; median age 45 years) stable non-cystic fibrosis bronchiectatic adult patients were enrolled into this study. Dyspnea scores, number of exacerbations and hospital admissions within the last year, body-mass index, pulmonary function tests, sputum cultures, bronchiectasis disease severity indexes (BSI and FACED) were assessed. Anxiety and depression were evaluated by using the Turkish version of the hospital anxiety and depression scale questionaire. Anxiety was diagnosed in 30% of patients and depression was diagnosed in 41% of the participants. Female participants had significantly higher rates of depression (55% vs. 22%; p= 0.002). Exacerbation rates within the last year were higher among the subjects with anxiety, moreover, patients with depression had shorter duration of disease. BSI and FACED severity indexes increased with longer duration of disease (5.6 ± 5.0 yrs in mild group vs. 10.1 ± 9.2 yrs in moderate-to-severe group, p= 0.035 and 5.7 ± 5.4 yrs in mild group vs. 12.1 ± 9.7 yrs in moderate-to-severe group, p= 0.001, respectively), however, anxiety and depression were not related with BSI and FACED severity indexes. Patients with non-cystic fibrosis bronchiectasis have an increased risk for depression and anxiety. Duration of disease and higher exacerbation rate are related with psychological status and indexes increased with longer duration of disease. Early detection and taking the necessary measures to improve the psychological state is necessary for the overall management of these patients.

Pregnancy Zone Protein Is Associated with Airway Infection, Neutrophil Extracellular Trap Formation, and Disease Severity in Bronchiectasis.

Rationale: PZP (pregnancy zone protein) is a broad-spectrum immunosuppressive protein believed to suppress T-cell function during pregnancy to prevent fetal rejection. It has not previously been reported in the airway.Objectives: To characterize PZP in the bronchiectasis airway, including its relationship with disease severity.Methods: Label-free liquid chromatography/mass spectrometry was performed for sputum protein profiling of patients with bronchiectasis confirmed by high-resolution computed tomography. Results for patients with and without Pseudomonas aeruginosa infection were compared. Sputum and serum PZP was measured by validated ELISA. Airway infection status was established by culture and 16S ribosomal RNA sequencing. Immunofluorescence, ELISA, and electron microscopy were used to identify the cellular source of PZP in neutrophils treated with multiple stimuli.Measurements and Main Results: Elevated PZP was identified by label-free liquid chromatography/mass spectrometry as being associated with P. aeruginosa infection. In a validation study of 124 patients, sputum but not serum concentrations of PZP were significantly associated with the Bronchiectasis Severity Index, the frequency of exacerbations, and symptoms. Airway infection with Proteobacteria such as P. aeruginosa was associated with higher concentrations of PZP. PZP in sputum was directly related to airway bacterial load. Neutrophils induced to form neutrophil extracellular traps (NETs) with phorbol myristate acetate released high concentrations of PZP in vitro, and fluorescence microscopy confirmed the presence of PZP in NETs, whereas fluorescence and electron microscopy localized PZP to the cytoplasm and nuclei of neutrophils. Effective antibiotic therapy reduced sputum PZP.Conclusions: PZP is released into NETs. We report a novel link between airway infection, NET formation, and disease severity in bronchiectasis during chronic airway inflammation.

Vitamin D and disease severity in bronchiectasis.

Bronchiectasis is a complex respiratory disease characterised by permanent dilatation of bronchi. Vitamin D plays a role in infective disease by modulating the inflammation. Patients affected by bronchiectasis are frequently Vitamin D deficient and it correlates with lung function decline. We want to understand if there is a correlation between Vitamin D and clinical and radiological severity of bronchiectasis. We included 57 patients (17 males/40 female with mean age 60 ± 12 years) between October 2017 and March 2018. We excluded patients with cystic fibrosis, traction bronchiectasis and reporting Vitamin D supplementation. Bronchiectasis severity index (BSI) and Bhalla score were calculated, blood inflammatory markers and Vit. D were measured and lung function tests were performed. Vitamin D is deficient in 64% of patients, sufficient in 36% and normal in 7%. Mean BSI is 7.5 ± 5 and mean Bhalla score is 16 ± 4. Vitamin D levels correlate with Bhalla score (R2 = 0.68, p < 0.001) and BSI (R2 = 0.58, p < 0.0001). The correlation appears to be stronger than other markers of inflammation such as ESR and CRP [R2 = 0.33, p = 0.001 and R2 = 0.39, p = 0.001 respectively]. We consider Vitamin D as a good predictor of clinical and radiological severity of bronchiectasis.

A qualitative synthesis of gastro-oesophageal reflux in bronchiectasis: Current understanding and future risk.

Gastro-oesophageal reflux disease (GORD) is a common comorbidity in bronchiectasis, and is often associated with poorer outcomes. The cause and effect relationship between GORD and bronchiectasis has not yet been fully elucidated and a greater understanding of the pathophysiology of the interaction and potential therapies is required. This review explores the underlying pathophysiology of GORD, its clinical presentation, risk factors, commonly applied diagnostic tools, and a detailed synthesis of original articles evaluating the prevalence of GORD, its influence on disease severity and current management strategies within the context of bronchiectasis. The prevalence of GORD in bronchiectasis ranges from 26% to 75%. Patients with co-existing bronchiectasis and GORD were found to have an increased mortality and increased bronchiectasis severity, manifest by increased symptoms, exacerbations, hospitalisations, radiological extent and chronic infection, with reduced pulmonary function and quality of life. The pathogenic role of Helicobacter pylori infection in bronchiectasis, perhaps via aspiration of gastric contents, also warrants further investigation. Our index of suspicion for GORD should remain high across the spectrum of disease severity in bronchiectasis. Identifying GORD in bronchiectasis patients may have important therapeutic and prognostic implications, although clinical trial evidence that treatment targeted at GORD can improve outcomes in bronchiectasis is currently lacking.

The BRICS (Bronchiectasis Radiologically Indexed CT Score): A Multicenter Study Score for Use in Idiopathic and Postinfective Bronchiectasis

The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis. The Bronchiectasis Radiologically Indexed CT Score (BRICS) was devised based on a multivariable analysis of the Bhalla score and its ability in predicting clinical parameters of severity. The score was then externally validated in six centers in 302 patients. A total of 184 high-resolution CT scans were scored for the validation cohort. In a multiple logistic regression model, disease severity markers significantly associated with the Bhalla score were percent predicted FEV1, sputum purulence, and exacerbations requiring hospital admission. Components of the Bhalla score that were significantly associated with the disease severity markers were bronchial dilatation and number of bronchopulmonary segments with emphysema. The BRICS was developed with these two parameters. The receiver operating-characteristic curve values for BRICS in the derivation cohort were 0.79 for percent predicted FEV1, 0.71 for sputum purulence, and 0.75 for hospital admissions per year; these values were 0.81, 0.70, and 0.70, respectively, in the validation cohort. Sputum free neutrophil elastase activity was significantly elevated in the group with emphysema on CT imaging. A simplified CT scoring system can be used as an adjunct to clinical parameters to predict disease severity in patients with idiopathic and postinfective bronchiectasis.

Microbiota composition and disease severity in bronchiectasis

The microbes present in the lower airways are strongly implicated in the development, progression, and severity of many types of chronic lung disease. Complex and bidirectional relationships exist between the airway environment, the composition of the lung microbiota, and rate and nature of accumulated damage. Understanding these interactions, and their implications for bronchiectasis, is challenging. The development of local immune regulation in early life, and the effects of host mutations, such as those affecting mucin properties, both influence airway microbiology. As disease develops, there is a divergence from healthy airway microbiology, while in later disease, changes in the physicochemical characteristics of the lungs due to inflammation and remodelling, as well as exposure to antibiotics and other therapies, are central in defining more marked changes in airway microbiology. Throughout this process, the impact of altered airway microbiology of respiratory health is influenced by both the behaviour and immune-modulatory traits of pathogenic taxa, and the interactions of these key species with the wider airway microbiota. Recent technological advances present opportunities for detailed characterisation of the airway microbiome, allowing us to dissect the relationships between airway microbiology and respiratory health. The ways in which this basic research can help to provide mechanistic insight, prognostic information, and a basis for improved clinical care, will be discussed.

Vitamin-D deficiency is associated with chronic bacterial colonisation and disease severity in bronchiectasis

IntroductionVitamin-D deficiency has been linked to an increased risk of respiratory infections. The objective of this study was to determine the frequency and clinical importance of vitamin-D deficiency in patients...

Elevated peripheral airway nitric oxide in bronchiectasis reflects disease severity

Bronchiectasis is characterised by neutrophilic bronchial inflammation and patients are prone to recurrent or chronic bacterial airway infections. Direct measurement of lung inflammation would be useful in order to assess disease activity and guide need for antibiotic treatment and to monitor response. Current methods of monitoring inflammation are invasive, indirect or insensitive. Exhaled nitric oxide (FE(NO)) is a direct simple non-invasive test of inflammation used in other airway diseases. The aim of this study was to test whether peripheral airway nitric oxide (C(alv)) can provide a clinically useful direct measure of inflammation in the lungs of patients with bronchiectasis. Fifty three patients with bronchiectasis were studied when clinically stable and a further 20 patients during an exacerbation of bronchiectasis. FE(NO) was measured by chemiluminescence using a NO analyser. Two models of pulmonary exchange dynamics were used to calculate proximal and peripheral contributions to final FE(NO) concentration. FE(NO) was elevated in bronchiectasis patients compared to 30 healthy controls (p < 0.05). Compartmental modelling reveals that this elevation is due to an increase in peripheral airway NO (bronchiectasis 3.6 ppb (2.1), controls 2.7 ppb (1.5) p < 0.05) whereas proximal airway NO levels are normal (bronchiectasis 777(751) pl/s, controls 582(579) pl/s ns). C(alv) relates to disease severity measured by lung function and HRCT scan and correlates with the quality of life score. There is no change in FE(NO) parameters at exacerbation and following treatment. Peripheral airway NO is elevated and reflects disease severity in bronchiectasis but does not provide information to inform acute treatment decisions.

Up-regulation of circulating adhesion molecules in bronchiectasis.

Adhesion molecules are expressed on the surface of endothelial cells and leukocytes and are responsible for mediating the migration of intravascular leukocytes into inflamed tissue. Intensive recruitment of neutrophils into the airways occurs in bronchiectasis, although little is known about the role of adhesion molecules in this process. The authors, therefore, determined serum levels of E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 in stable bronchiectasis patients (n=37) and healthy control subjects (n=17), and evaluated their relationship with clinical markers of disease severity in bronchiectasis. Serum levels of E-selectin, ICAM-1 and VCAM-1 in bronchiectasis patients were significantly higher than those in control subjects (p=0.02, <0.0001 and 0.0002 respectively). Both E-selectin and ICAM-1 levels were inversely related to forced expiratory volume in one second (FEV1)% predicted (r=-0.57, p<0.001; and r=-0.53, p=0.001 respectively), and FVC% predicted (r=-0.52, p=0.002; and r=-0.46, p=0.005). This was not the case for VCAM-1 levels. There was a correlation between serum ICAM-1 levels and 24 h sputum volume (r=0.34, p= 0.04). Serum E-selectin and ICAM-1, but not VCAM-1, levels showed correlation with the number of lung lobes affected by bronchiectasis (r=0.35, p=0.04 and r=0.34, p=0.04 respectively). These original observations strongly suggest that E-selectin, intercellular adhesion molecule-1 and Vascular adhesion molecule-1 could play a significant role in the pathogenesis of bronchiectasis.