Clinical outcomes of long-term inhaled combination therapies in patients with bronchiectasis and airflow obstruction.

BACKGROUND AND OBJECTIVES: Few studies have reported which inhaled combination therapy, either bronchodilators and/or inhaled corticosteroids (ICSs), is beneficial in patients with bronchiectasis and airflow obstruction. Our study compared the efficacy and safety among different inhaled combination therapies in patients with bronchiectasis and airflow obstruction. METHODS: Our retrospective study analyzed the patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity < 0.7 and radiologically confirmed bronchiectasis in chest computed tomography between January 2005 and December 2021. The eligible patients underwent baseline and follow-up spirometric assessments. The primary endpoint was the development of a moderate-to-severe exacerbation. The secondary endpoints were the change in the annual FEV1 and the adverse events. Subgroup analyses were performed according to the blood eosinophil count (BEC). RESULTS: Among 179 patients, the ICS/long-acting beta-agonist (LABA)/long-acting muscarinic antagonist (LAMA), ICS/LABA, and LABA/LAMA groups were comprised of 58 (32.4%), 52 (29.1%), and 69 (38.5%) patients, respectively. ICS/LABA/LAMA group had a higher severity of bronchiectasis and airflow obstruction, than other groups. In the subgroup with BEC ≥ 300/uL, the risk of moderate-to-severe exacerbation was lower in the ICS/LABA/LAMA group (adjusted HR = 0.137 [95% CI = 0.034-0.553]) and the ICS/LABA group (adjusted HR = 0.196 [95% CI = 0.045-0.861]) compared with the LABA/LAMA group. The annual FEV1 decline rate was significantly worsened in the ICS/LABA group compared to the LABA/LAMA group (adjusted ß-coefficient=-197 [95% CI=-307--87]) in the subgroup with BEC < 200/uL. CONCLUSION: In patients with bronchiectasis and airflow obstruction, the use of ICS/LABA/LAMA and ICS/LABA demonstrated a reduced risk of exacerbation compared to LABA/LAMA therapy in those with BEC ≥ 300/uL. Conversely, for those with BEC < 200/uL, the use of ICS/LABA was associated with an accelerated decline in FEV1 in comparison to LABA/LAMA therapy. Further assessment of BEC is necessary as a potential biomarker for the use of ICS in patients with bronchiectasis and airflow obstruction.

Risk Factors of Chronic Pulmonary Aspergillosis in Patients with Etiology Positive Pulmonary Tuberculosis.

Objective: Pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) have many similarities in clinical symptoms. In patients with etiology-positive pulmonary tuberculosis (EPTB), Aspergillus infection is easily overlooked, and missed diagnosis occurs. We attempted to analyze the clinical characteristics and risk factors of EPTB combined with CPA (EPTB-CPA), and to suggest to clinicians the possibility of CPA in EPTB patients. Methods: 58 patients with EPTB-CPA diagnosed and treated in Wuhan Pulmonary Hospital from April 2021 to March 2022 were retrospectively collected as the case group. According to the age group of the case group, 174 patients with EPTB were randomly selected as the control group at a ratio of 1:3. Multivariate logistic regression analysis was utilized to analyze the risk factors. Results: Multivariate Logistic regression analysis was performed on the pulmonary cavity, chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, lung damage, anemia, and hypoproteinemia. Among them, pulmonary cavity (P = .001), COPD (P = .006), and bronchiectasis (P = .020) were statistically significant. Conclusion: Our findings suggest that when EPTB patients present with pulmonary cavities and comorbidities such as COPD or bronchiectasis, clinicians should consider the possibility of CPA. Identifying these risk factors can help improve the accuracy of diagnosis and facilitate early detection and management of EPTB-CPA.

Evaluation of high dose N- Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study.

BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis. AIMS: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects. METHODS: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed. RESULTS: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups. CONCLUSION: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.

[Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis (2023)].

Cystic fibrosis (CF) is one of the most common autosomal recessive genetic diseases in Caucasians, but CF patients in China are rare, and it was listed as the first batch of rare diseases in China in 2018. In recent years, CF has been gradually recognized in China, and the number of CF patients reported in China in the past 10 years is more than 2.5 times the total number in the previous 30 years, and the total number of CF patients is estimated to be more than 20 000. The research progress of CF gene modification has led to the innovation of CF treatment. However, the sweat test as an important test for the diagnosis of CF has not been widely implemented in China. At present, the diagnosis and treatment of CF in China still lacks standardized recommendations. In view of these updates, the Chinese Experts Cystic Fibrosis Consensus Committee has formed "the Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis" based on extensive opinion gathering, literatures review, multiple meetings and discussions. This consensus collects 38 core issues related to CF, including pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and patient management. Finally, 32 recommendations were formulated. The consensus used the modified GRADE methodology to grade the evidence evaluation and recommendations. This is the current state of CF consensus in China, and we hope to improve the diagnosis and treatment of CF in China in the future.Summary of recommendationsQuestion 1: How can CF be identified?CF should be suspected if there is: (1) a family history of CF; (2) delayed meconium expulsion or meconium ileus; (3) pancreatic exocrine insufficiency, mainly characterized by long-standing steatorrhea and malnutrition; (4) recurrent lower respiratory tract infections of infantile onset, especially Pseudomonas aeruginosa (PA), Staphylococcus aureus infections of respiratory aetiology; (5) chronic sinusitis, especially when combined with juvenile presentation of nasal polyps; (6) chest CT abnormalities such as the presence of air trapping, bronchiectasis (upper lobe predominant); (7) pseudo-Bartter syndrome; (8) absence of vas deferens in males; (9) clubbing in young bronchiectasis patients(1C).Question 2: What are the diagnostic criteria for CF?1.1 Presence of one or more of the characteristic clinical manifestations or family history consistent with CF, and meeting at least one of the following definite diagnostic criteria in 1.2 or 1.3.1.2 Sweat chloride testing:(1) Concentrations of more than 60 mmol/L are diagnostic; (2) concentrations between 30-59 mmol/L are intermediate, and genetic variation must be considered to confirm the diagnosis; (3) concentrations less than 30 mmol/L are considered normal.1.3 Genetic testing:(1) Detection of two disease-causing CFTR(cystic fibrosis transmembrane conductance regulator) mutations on biallelic alleles; (2) The CFTR variants are of undetermined significance, but tests such as sweat chloride concentration, intestinal current measurement, or nasal mucosal potential difference suggest abnormal CFTR function, then CF is diagnostic(1C).Question 3: What is the diagnostic process for CF arranged?Sweat chloride testing and CFTR gene analysis are recommended in all patients suspected of CF(1D).Question 4: What is the value of sweat chloride testing in the diagnosis of CF?Sweat chloride testing is the gold standard for the clinical diagnosis of CF(1C).Question 5: What is the value of CFTR genetic testing in Chinese CF diagnosis?Biallelic pathogenic variants of CFTR are a definitive diagnosis of CF(1D).Question 6: What is the diagnostic value of imaging for CF?Chest CT is a sensitive test for early stages of lung disease in patients with CF and is appropriate in younger patients and to assess disease progression. The imaging findings of abdominal visceral involvement in CF lack specificity(2C).Question 7: How to evaluate the pancreatic function of CF patients?Fecal elastase may be used as the first indicator to assess pancreatic exocrine function in patients with CF (2C).Question 8: How to diagnose hepatic abnormality of CF?CF related liver disease was diagnosed when CF was confirmed and 2 of the following 4 criteria were met: (1) hepatomegaly and/or splenomegaly confirmed by ultrasound; (2) ALT, AST, and GGT on three consecutive occasions above the upper limit of normal on three consecutive occasions for more than 12 months and excluding other causes; (3) had evidence of liver involvement, portal hypertension, or bile duct dilatation by ultrasound; (4) liver biopsy confirmation (focal biliary cirrhosis or multilobular cirrhosis) may be indicated if the diagnosis is suspected(2D).Question 9: How to identify pulmonary exacerbations in patients with CF?Pulmonary exacerbations are indicated when any 4 of the following 12 signs or symptoms are met: increased sputum; new onset haemoptysis or increased haemoptysis; exacerbation of cough; increased dyspnea; malaise, fatigue, or somnolence; body temperature above 38 ℃; anorexia or weight loss; sinus pain or tenderness; increased sinus secretions; new chest signs; FEV1≥10% decline from previous; imaging changes suggestive of pulmonary infection(2D).Question 10: How to diagnose CF related diabetes?Diagnostic criteria for CF related diabetes are the same as those for diabetes in the population(1D).Question 11: How to evaluate the nutritional status of CF patients?Anthropometric parameters reflecting nutritional status should be assessed regularly. And the goal of nutritional assessment is to evaluate and monitor whether pediatric patients are achieving normal standards of growth and development or whether adult patients are maintaining adequate nutritional status(1C).Question 12: Does CF require pathological examination as a diagnostic basis?Pathohistological biopsy is not recommended as a first-line diagnostic method in patients with a suspected diagnosis of CF(1D).Question 13: Do CF patients need long-term macrolides?At least 6 months of azithromycin treatment is recommended for CF patients with chronic PA infection(2A).Question 14: Do CF patients need long-term inhalation of hypertonic saline?Long term treatment with hypertonic saline is recommended for patients with CF(1A).Question 15: Do CF patients need long-term inhalation of Dornase alfa(DNase)?Long term use of DNase is recommended in patients with CF aged 6 years and older(1A).Question 16: Do CF patients need inhalation of mannitol?Inhaled mannitol therapy is recommended for more than 6 months in patients with CF aged 18 years and older when other inhaled treatments are unavailable or intolerable(2A).Question 17: How to deal with PA found in the sputum culture of CF patients?When sputum cultures from patients with CF are positive for PA, it needs to determine the characteristics of the infection first. The purpose for acute infection is to eradicate PA. Chronic colonization does not need to be eradicated, and the main purpose is to reduce the bacterial load and improve symptoms(1A).Question 18: Do CF patients need inhalation of antibiotics?Inhaled antibiotic therapy is recommended for CF patients with PA infection(1A).Question 19: Do CF patients need inhaled or systemic corticosteroids?In patients with CF without asthma or ABPA, routine inhaled or systemic glucocorticoids are not recommended (2A).Question 20: Do CF patients need to inhale bronchodilators?Bronchodilators can be used in the short term to improve symptoms in patients with CF in the presence of airway obstruction, but the long-term benefit is insufficient (2B).Question 21: Do CF patients need expectorant medicine?Patients with CF can take acetylcysteine orally or aerosolized(2A).Question 22: How to deal with acute pulmonary exacerbation in CF patients?Intensive implementation of non-antimicrobial therapy is recommended during pulmonary exacerbations in patients with CF. Antimicrobials with activity against PA were selected for empirical treatment, and the treatment was adjusted according to the results of bacterial culture and drug susceptibility testing. A 21-day long course of anti-infective therapy is not recommended(1B).Question 23: How to treat CF patients with ABPA?Medical therapy is recommended for CF patients with ABPA who meet any of the following criteria: patients with elevated immunoglobulin E levels and concomitant worsening of pulmonary function and/or pulmonary symptoms, or imaging suggesting new infiltrative foci in the chest(1D).Glucocorticoids are recommended for ABPA exacerbations in CF patients without contraindications(2D).Itraconazole should be added if the patient presents with poor response to corticosteroids, recurrence of ABPA, corticosteroid dependence, or corticosteroid toxicity(2D).Question 24: Is lung transplantation recommended for patients with CF? When is it recommended?Patients with CF may be evaluated for lung transplantation when they meet the following criteria after optimal medical therapy: (1) FEV1<30% predicted; (2) FEV1<40% predicted (<50% predicted in children) with the following: 6-minute walk distance<400 meters; PaCO2>50 mmHg(1 mmHg=0.133 kPa); hypoxia at rest or after activity; pulmonary artery pressure measured by cardiotocography>50 mmHg or right heart dysfunction; continued deterioration despite aggressive supplementation of nutritional support; two exacerbations requiring intravenous antibiotic therapy per year; massive hemoptysis (>240 ml) requiring pulmonary artery embolization; presented with pneumothorax; (3) FEV1<50% predicted and rapid decline in lung function or rapid worsening of symptoms; (4) Presented with an acute exacerbation requiring positive pressure mechanical ventilation(2C).Question 25: How to deal with pancreatic disease in CF patients?Pancreatic enzyme replacement therapy is recommended in patients with CF pancreatic disease(1A).Question 26:How to deal with hepatobiliary disease in CF patients?Ursodeoxycholic acid is not recommended in asymptomatic patients with CF hepatobiliary disease(2B).Question 27: How to deal with gastrointestinal problems such as acid regurgitation in CF patients?Acid suppression is recommended for CF patients with gastrointestinal symptoms such as acid regurgitation (2B).Question 28: How to deal with CF related diabetes?Insulin therapy is recommended in CF related diabetes(1B).Question 29: How should nutritional support be given to patients with CF?Energy intake in patients with CF is recommended to be 110%-200% of the energy requirement of a healthy person under equivalent physiological conditions. And maintaining adequate protein, appropriate intake of fats, electrolytes, and fat-soluble vitamins are recommanded(1A).Question 30: How should respiratory rehabilitation be performed in patients with CF?Airway clearance therapy and appropriate exercise are recommended for patients with CF(1A).Question 31: What is included in the follow-up of CF patient?Patients with CF should have regular follow-up. Adult patients are recommended to be followed every 3-6 months, and children should be followed more frequently(2A).Question 32: How should CF patients avoid infections?Inpatients and outpatients are recommended to be separated according to microbiota carriage status(1D).Good hand hygiene is recommended for the patients with CF and their contacts(1D).It is recommended that CF patients wear masks in healthcare settings. This may reduce the release of potentially infectious aerosols during coughing (1D).Annual influenza vaccination is recommended for patients with CF>6 months of age and for all family members of patients with CF and all healthcare workers caring for these patients(2D).Palivizumab may be considered for the prevention of respiratory syncytial virus infection in patients with CF under two years of age(2A).

'The likes of me running and walking? No chance': Exploring the perceptions of adult patients with bronchiectasis towards exercise.

Objective: To explore the views and experiences of adult patients with bronchiectasis towards exercise. Methods: Semi-structured interviews with ten patients with bronchiectasis were conducted to explore perceptions of exercise, potential barriers and facilitators of exercise. Inductive thematic analysis was used to identify key themes. Findings: Five main themes: 1. The language of exercise 2. Facilitators to exercise 3. Barriers to exercise 4. Exercise has a positive impact on health and life expectancy 5. Grief regarding loss of ability Discussion: Participants perceived exercise as positive, but there was variance regarding what this entailed. Findings suggest healthcare professionals should consider the language used when prescribing exercise and provide clarity for patients and reflect on their own role in advising on exercise. There were both common and differing barriers and facilitators to exercise between participants. Holistic needs and the identification of these potential barriers and facilitators to exercise could aid compliance. Further research is needed to explore generalisability and the effectiveness of behaviour change models to improve engagement with exercise.

Tea consumption and risk of lower respiratory tract infections: a two-sample mendelian randomization study.

BACKGROUND: Observational studies have reported the association between tea consumption and the risk of lower respiratory tract infections (LRTIs). However, a consensus has yet to be reached, and whether the observed association is driven by confounding factors or reverse causality remains unclear. METHOD: A two-sample Mendelian randomization (MR) analysis was conducted to determine whether genetically predicted tea intake is causally associated with the risk of common LRTI subtypes. Genome-wide association study (GWAS) from UK Biobank was used to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea intake each day. The summary statistics for acute bronchitis, acute bronchiolitis, bronchiectasis, pneumonia, and influenza and pneumonia were derived from the FinnGen project. RESULTS: We found that genetically predicted an extra daily cup of tea intake was causally associated with the decreased risk of bronchiectasis [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.47-0.78, P < 0.001], pneumonia (OR = 0.90, 95% CI = 0.85-0.96, P = 0.002), influenza and pneumonia (OR = 0.91, 95% CI = 0.85-0.97, P = 0.002), but not with acute bronchitis (OR = 0.91, 95% CI = 0.82-1.01, P = 0.067) and acute bronchiolitis (OR = 0.79, 95% CI = 0.60-1.05, P = 0.100). Sensitivity analyses showed that no heterogeneity and pleiotropy could bias the results. CONCLUSIONS: Our findings provided new evidence that genetically predicted an extra daily cup of tea intake may causally associated with a decreased risk of bronchiectasis, pneumonia, and influenza and pneumonia.

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC): can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial.

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20-365 from study allocation and (ii) days alive and without exacerbation within days 20-365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142 . Registered on August 25, 2017.

Video game-based exercise in children and adolescents with non-cystic fibrosis bronchiectasis: A randomized comparative study of aerobic and breathing exercises.

BACKGROUND: Video game-based systems have been proposed to improve effectiveness and compliance with exercise training in children and adolescents with noncystic fibrosis bronchiectasis (NCFB). This study aimed to investigate the effects of aerobic and breathing video game-based exercises (VGE) on pulmonary function, respiratory and peripheral muscle strength, functional capacity, and balance in children and adolescents with NCFB. METHOD: Thirty-nine children and adolescents aged between 8 and 18 years with NCFB were randomly allocated into three groups as "home-based chest physiotherapy group" (CP), "aerobic VGE given in addition to home-based chest physiotherapy group" (CP + aerobic VGE), and "breathing VGE given in addition to home-based chest physiotherapy group" (CP + breathing VGE). All three groups performed chest physiotherapy program twice a day for 7 days per week for 8 weeks. Pulmonary function, respiratory and peripheral muscle strength, functional capacity, and balance were assessed at baseline and after 8 weeks of training. RESULTS: The improvement in maximum expiratory pressure and balance scores were significantly higher in both CP + aerobic and CP + breathing VGE groups. The significant improvement in maximum inspiratory pressure was greater in the CP + breathing VGE group. The changes in peripheral muscle strength and functional capacity were significantly higher in the CP + aerobic VGE group. CONCLUSIONS: The present study showed that aerobic VGE provides additional benefits in improving peripheral muscle strength and functional capacity, while breathing VGE provides further increase in improving respiratory muscle strength. In addition, both aerobic and breathing VGE were effective in improving balance, but they were not superior to each other.

Embolization with more diluted glue-lipiodol in patients with massive hemoptysis: single center experience results.

OBJECTIVE: The aim of the study was to demonstrate the efficacy and safety of bronchial artery embolization (BAE) with more diluted N-butyl-2- cyanoacrylate (NBCA) in patients with massive hemoptysis. PATIENTS AND METHODS: In this retrospective study, there are 48 patients who underwent NBCA and BAE for massive hemoptysis between March 2018 and September 2021. Demographic data, technical and clinical results, immediate hemoptysis control, recurrent hemoptysis and complications were evaluated. RESULTS: The technical success rate and immediate hemoptysis control were achieved in 97.9% and 93.7%, respectively. The 3 patients who were exitus within the first 10 days were removed from the follow-up range. During the follow-up period (range, 5 months-42 months; median, 27.5 months), recurrent hemoptysis was found in 3 of the 45 patients (6.6 %). Since 1 patient refused and one patient died within the first 24 hours, repeated BAE procedures were performed in 4 patients. A total of 55 sessions of BAE with NBCA was performed to 48 patients. The underlying diseases causing hemoptysis were determined to be bronchiectasis (n=16), tuberculosis (n=8), neoplasm (n=7), aspergilloma (n=3), and arteriovenous malformation (n=2). In 4 patients, bronchiectasis and tuberculosis were present together and in 8 patients, the cause could not be specified. CONCLUSIONS: In conclusion, BAE with more diluted NBCA is a safe and effective embolization method. In addition, the use of more diluted NBCA reduces the recurrence rates in patients with hemoptysis.

Medical nutrition therapy in hemodynamically unstable patients due to cardiogenic shock with infected bronchiectasis and severe protein-energy malnutrition.

OBJECTIVE: Cardiogenic shock is defined as tissue hypoperfusion due to cardiac dysfunction. It is associated with hemodynamic unstability and elevated arterial lactate as one indicator for anaerobic metabolism. Hypercatabolic state in this condition leads to increasing nutritional requirement and negative nitrogen balance. Therefore, medical nutrition therapy by considering metabolic tolerance can prevent further metabolic deterioration and loss of lean mass and improve the patient's clinical outcome. METHODS: A 44-years-old female patient with severe protein-energy malnutrition (Subjective Global Assessment Score C; MUAC 15cm) suffered from hemodynamic unstability due to cardiogenic shock and infected bronchiectasis at the infection center of Wahidin Sudirohusodo Hospital. Intake was postponed due to mean arterial pressure 56mmHg on vasopressor support and oxygen saturation below 93%. Physical examinations showed loss of subcutaneous fat, lung crackles and wheezing, muscle wasting, and pretibial edema. Laboratory assessments showed elevated arterial lactate (3.2mmol/L), hypoalbuminemia (2.4g/dL), lymphocytopenia (650/µL), elevated liver enzymes (SGOT 780U/L; SGPT 868U/L), and urine urea nitrogen (5g/24h). Nutritional therapy was started after mean arterial pressure ≥65mmHg with a stable dosage of the vasopressor drug and decreased arterial lactate level to 2.2mmol/L then given gradually with a target calorie of 1500kcal and protein 1.5-1.8g/kg ideal body weight/day using high protein diet. Arterial lactate and blood gass analyses were controlled every day to determine the target of nutritional therapy day by the day. Snakehead fish extract, zinc, vitamin B complex, Thiamine, vitamin C, vitamin A, vitamin D3, and Curcumin were supplied. RESULT: After 15 days of nutritional therapy, the patient was discharged from the hospital with stable hemodynamic without vasopressor support, adequate nutritional intake, improvement of anthropometric parameters, and laboratory test results (arterial lactate 1.6mmol/L, albumin 3.1g/dL, lymphocyte 1.871/µL, SGOT 34U/L, SGPT 41U/L, urine urea nitrogen 0.72g/24h). CONCLUSION: Adequate nutritional therapy, which is planned by evaluating hemodynamic tolerance, can improve patient clinical outcomes and positive nitrogen balance in the hemodynamically unstable patient.

Medical nutritional therapy in infected bronchiectasis with impending respiratory failure: A case report.

OBJECTIVE: Bronchiectasis is a chronic infective and inflammatory respiratory disease that causes significant morbidity and mortality. Repeated respiratory infections may lead to infected bronchiectasis (IB) and acute exacerbations which often require hospital admission, increase risk of malnutrition and impact quality of life and eventually leads to death. Nutritional therapy is needed to modulate inflammation and enhance immunity to reduce severity of exacerbation, overcome malnutrition, as well as to decrease morbidity and mortality. METHODS: A 59-year-old female patient, diagnosed with IB. The patient had low oral intake due to productive cough and anorexia since 2 weeks before admission. Moreover, she had gradual shortness of breath that caused an impending respiratory failure during hospitalization, supported by continuous positive airway pressure (CPAP). Nutritional assessment was made based on Subjective Global Assessment (SGA) score C. Abnormal laboratory findings seen were increased in neutrophil-to-lymphocyte ratio (NLR) 9.3, moderate depletion of immune system with total lymphocyte count (TLC) 808.4/µl, hypoalbuminemia (3.2g/dl) and increased in liver enzymes: aspartate aminotransferase (AST) 206U/l, Alanine aminotransferase (ALT) 224U/l. Nutritional therapy was given gradually with target calorie 1400-1900kcal, protein 0.8-1.5g/kg IBW/day, carbohydrates 45-50%, and fat 33.3-43% through oral and parenteral nutrition. The patient was given supplementations such as vitamins (A, B complex, C, D), zinc, curcumin and snakehead fish extract high albumin content. RESULT: After 14 days of treatment, significant clinical and metabolic improvement in NLR, TLC, plasma albumin, liver enzymes (AST/ALT), blood gas analysis, and functional capacity (handgrip strength) were found. CONCLUSION: An adequate nutritional therapy with macro and micro-nutrients in IB patient can improve clinical outcome, nutritional status and quality of life.

Risk of Severe Bleeding With Extended Rivaroxaban to Prevent Venous Thromboembolism in Acute Medically Ill Patients With Bronchiectasis.

Background: Bronchiectasis is a chronic inflammation of the bronchi with recurrent infections and hemoptysis. The MAGELLAN study compared oral rivaroxaban, 10 mg once daily (QD), for 35 ± 4 days with subcutaneous enoxaparin 40 mg QD for 10 ± 4 days followed by placebo for 25 ± 4 days to prevent venous thromboembolism in patients hospitalized with an acute medical illness. MAGELLAN included a subset of patients with bronchiectasis. In a post hoc analysis, we evaluated the incidence and severity of pulmonary bleeding in patients with bronchiectasis who were hospitalized for an acute medical illness. This analysis included MAGELLAN patients diagnosed with bronchiectasis at baseline. Patients were evaluated by treatment group for International Society on Thrombosis and Haemostasis major bleeding, non-major clinically relevant (NMCR) bleeding, and the composite of the 2 (ie, clinically relevant bleeding). Results: Medically ill patients with bronchiectasis were randomized to rivaroxaban (n = 60) or enoxaparin/placebo (n = 61). There were 2 fatal pulmonary bleeds and 1 fatal gastrointestinal bleed in the rivaroxaban arm and no fatal or major bleeding in the enoxaparin/placebo arm. The incidence of major bleeding was 5% in the rivaroxaban arm. One NMCR bleed occurred in the rivaroxaban arm and 2 NMCR bleeds occurred in the enoxaparin/placebo arm. The incidence of clinically relevant bleeding was 6.7% versus 3.3% in the rivaroxaban and enoxaparin/placebo groups, respectively (relative risk = 2.06 [95% confidence interval: 0.351-12.046]). Conclusion: In-patients hospitalized with bronchiectasis and an acute medical illness, clinically relevant bleeding, including fatal pulmonary hemorrhage, occurs more frequently with extended rivaroxaban thromboprophylaxis than with enoxaparin followed by placebo.

The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update.

Pseudomonas aeruginosa is a Gram-negative bacterial pathogen that is a common cause of nosocomial infections, particularly pneumonia, infection in immunocompromised hosts, and in those with structural lung disease such as cystic fibrosis. Epidemiological studies have identified increasing trends of antimicrobial resistance, including multi-drug resistant (MDR) isolates in recent years. P. aeruginosa has several virulence mechanisms that increase its ability to cause severe infections, such as secreted toxins, quorum sensing and biofilm formation. Management of P. aeruginosa infections focuses on prevention when possible, obtaining cultures, and prompt initiation of antimicrobial therapy, occasionally with combination therapy depending on the clinical scenario to ensure activity against P. aeruginosa. Newer anti-pseudomonal antibiotics are available and are increasingly being used in the management of MDR P. aeruginosa.

The rough inhalable ciprofloxacin hydrochloride microparticles based on silk fibroin for non-cystic fibrosis bronchiectasis therapy with good biocompatibility.

Non-cystic fibrosis bronchiectasis (NCFB) is a chronic respiratory disease, and the thick and viscous mucus covering on respiratory epithelia can entrap the inhaled drugs, resulting in compromised therapeutic efficiency. In order to solve this problem, the inhalable ciprofloxacin hydrochloride microparticles (CMs) based on silk fibroin (SF) and mannitol (MAN) were designed and developed. SF was applied to increase the loading efficiency of ciprofloxacin hydrochloride by strong electrostatic interactions. MAN could facilitate the penetration of drugs through mucus, which ensured the drugs could reach their targets before clearance. Furthermore, the aerodynamic performance of the inhalable microparticles could be tuned by changing the surface roughness to achieve a high fine particle fraction value (45.04%). The antibacterial effects of CMs were also confirmed by measuring the minimum inhibitory concentration against four different bacteria strains. Moreover, a series of experiments both in vitro and in vivo showed that CMs would not affect the lung function and induce the secretion of inflammatory cytokines in lungs, demonstrating their excellent biocompatibility and biosafety. Therefore, CMs might be a promising pulmonary drug delivery system for the treatment of NCFB.

Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment.

PURPOSE: Ciprofloxacin (CIP) has poor lung targeting after oral inhalation. This study developed optimized inhalable nanostructured lipid carriers (NLCs) for CIP to enhance deposition and accumulation in deeper parts of the lungs for treatment of noncystic fibrosis bronchiectasis (NCFB). METHODS: NLC formulations based on stearic acid and oleic acid were successfully prepared by hot homogenization and in vitro-characterized. CIP-NLCs were formulated into nanocomposite micro particles (NCMPs) for administration in dry powder inhalation (DPI) formulations by spray-drying (SD) using different ratios of chitosan (CH) as a carrier. DPI formulations were evaluated for drug content and in vitro deposition, and their mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD), and emitted dose (ED) were determined. RESULTS: The CIP-NLCs were in the nanometric size range (102.3 ± 4.6 nm), had a low polydispersity index (0.267 ± 0.12), and efficient CIP encapsulation (98.75% ± 0.048%), in addition to a spherical and smooth shape with superior antibacterial activity. The in vitro drug release profile of CIP from CIP-NLCs showed 80% release in 10 h. SD of CIP-NLCs with different ratios of CH generated NCMPs with good yield (>65%). The NCMPs had a corrugated surface, but with increasing lipid:CH ratios, more spherical, smooth, and homogenous NCMPs were obtained. In addition, there was a significant change in the FPF with increasing lipid:CH ratios (P ˂ 0.05). NCMP-1 (lipid:CH = 1:0.5) had the highest FPD (45.0 µg) and FPF (49.2%), while NCMP-3 (lipid:CH = 1:1.5) had the lowest FPF (37.4%). All NCMP powders had an MMAD in the optimum size range of 3.9-5.1 µm. CONCLUSION: Novel inhalable CIP NCMP powders are a potential new approach to improved target ability and delivery of CIP for NCFB treatment.

The Effect of a High-Intensity PrO2Fit Inspiratory Muscle Training Intervention on Physiological and Psychological Health in Adults with Bronchiectasis: A Mixed-Methods Study.

Bronchiectasis is characterised by airflow obstruction and hyperinflation resulting in respiratory muscle weakness, and decreased exercise capacity. Inspiratory muscle training (IMT) is potentially an alternative treatment strategy to enhance respiratory muscle strength and endurance. Therefore, the aim was to investigate the effects of IMT on those with bronchiectasis. Eighteen participants (10 bronchiectasis) took part in an eight-week, three times a week IMT programme at 80% sustained maximal inspiratory pressure (SMIP). Lung function, respiratory muscle strength and endurance, exercise capacity, physical activity and self-determination theory measures were taken. Participants also took part in a semi-structured interview to assess their perceptions and experience of an IMT intervention. After eight weeks of IMT, bronchiectasis and healthy participants exhibited significant increases in MIP (27% vs. 32%, respectively), SMIP (16% vs. 17%, respectively) and inspiratory duration (36% vs. 30%, respectively). Healthy participants exhibited further improvements in peak expiratory flow and maximal oxygen consumption. Bronchiectasis participants reported high levels of perceived competence and motivation, reporting higher adherence and improved physical ability. Eight weeks of IMT increased inspiratory muscle strength and endurance in those with bronchiectasis. IMT also had a positive effect on perceived competency and autonomy, with bronchiectasis participants reporting improved physical ability and motivation, and high adherence.

Exercise training for bronchiectasis.

BACKGROUND: Bronchiectasis is characterised by excessive sputum production, chronic cough, and acute exacerbations and is associated with symptoms of dyspnoea and fatigue, which reduce exercise tolerance and impair quality of life. Exercise training in isolation or in conjunction with other interventions is beneficial for people with other respiratory diseases, but its effects in bronchiectasis have not been well established. OBJECTIVES: To determine effects of exercise training compared to usual care on exercise tolerance (primary outcome), quality of life (primary outcome), incidence of acute exacerbation and hospitalisation, respiratory and mental health symptoms, physical function, mortality, and adverse events in people with stable or acute exacerbation of bronchiectasis. SEARCH METHODS: We identified trials from the Cochrane Airways Specialised Register, ClinicalTrials.gov, and the World Health Organization trials portal, from their inception to October 2020. We reviewed respiratory conference abstracts and reference lists of all primary studies and review articles for additional references. SELECTION CRITERIA: We included randomised controlled trials in which exercise training of at least four weeks' duration (or eight sessions) was compared to usual care for people with stable bronchiectasis or experiencing an acute exacerbation. Co-interventions with exercise training including education, respiratory muscle training, and airway clearance therapy were permitted if also applied as part of usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected trials for inclusion, extracted outcome data, and assessed risk of bias. We contacted study authors for missing data. We calculated mean differences (MDs) using a random-effects model. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included six studies, two of which were published as abstracts, with a total of 275 participants. Five studies were undertaken with people with clinically stable bronchiectasis, and one pilot study was undertaken post acute exacerbation. All studies included co-interventions such as instructions for airway clearance therapy and/or breathing strategies, provision of an educational booklet, and delivery of educational sessions. The duration of training ranged from six to eight weeks, with a mix of supervised and unsupervised sessions conducted in the outpatient or home setting. No studies of children were included in the review; however we identified two studies as currently ongoing. No data were available regarding physical activity levels or adverse events. For people with stable bronchiectasis, evidence suggests that exercise training compared to usual care improves functional exercise tolerance as measured by the incremental shuttle walk distance, with a mean difference (MD) between groups of 87 metres (95% confidence interval (CI) 43 to 132 metres; 4 studies, 161 participants; low-certainty evidence). Evidence also suggests that exercise training improves six-minute walk distance (6MWD) (MD between groups of 42 metres, 95% CI 22 to 62; 1 study, 76 participants; low-certainty evidence). The magnitude of these observed mean changes appears clinically relevant as they exceed minimal clinically important difference (MCID) thresholds for people with chronic lung disease. Evidence suggests that quality of life improves following exercise training according to St George's Respiratory Questionnaire (SGRQ) total score (MD -9.62 points, 95% CI -15.67 to -3.56 points; 3 studies, 160 participants; low-certainty evidence), which exceeds the MCID of 4 points for this outcome. A reduction in dyspnoea (MD 1.0 points, 95% CI 0.47 to 1.53; 1 study, 76 participants) and fatigue (MD 1.51 points, 95% CI 0.80 to 2.22 points; 1 study, 76 participants) was observed following exercise training according to these domains of the Chronic Respiratory Disease Questionnaire. However, there was no change in cough-related quality of life as measured by the Leicester Cough Questionnaire (LCQ) (MD -0.09 points, 95% CI -0.98 to 0.80 points; 2 studies, 103 participants; moderate-certainty evidence), nor in anxiety or depression. Two studies reported longer-term outcomes up to 12 months after intervention completion; however exercise training did not appear to improve exercise capacity or quality of life more than usual care. Exercise training reduced the number of acute exacerbations of bronchiectasis over 12 months in people with stable bronchiectasis (odds ratio 0.26, 95% CI 0.08 to 0.81; 1 study, 55 participants). After an acute exacerbation of bronchiectasis, data from a single study (N = 27) suggest that exercise training compared to usual care confers little to no effect on exercise capacity (MD 11 metres, 95% CI -27 to 49 metres; low-certainty evidence), SGRQ total score (MD 6.34 points, 95%CI -17.08 to 29.76 points), or LCQ score (MD -0.08 points, 95% CI -0.94 to 0.78 points; low-certainty evidence) and does not reduce the time to first exacerbation (hazard ratio 0.83, 95% CI 0.31 to 2.22). AUTHORS' CONCLUSIONS: This review provides low-certainty evidence suggesting improvement in functional exercise capacity and quality of life immediately following exercise training in people with stable bronchiectasis; however the effects of exercise training on cough-related quality of life and psychological symptoms appear to be minimal. Due to inadequate reporting of methods, small study numbers, and variation between study findings, evidence is of very low to moderate certainty. Limited evidence is available to show longer-term effects of exercise training on these outcomes.

Effects of a Mixture of Ivy Leaf Extract and Coptidis rhizome on Patients with Chronic Bronchitis and Bronchiectasis.

BACKGROUND: Hederacoside C from ivy leaf dry extracts (HH) and berberine from Coptidis rhizome dry extracts (CR) can be combined (HHCR) as a herbal product. Previous studies have demonstrated that HHCR has antitussive and expectorant effects in animal models of respiratory disease. However, the therapeutic effects of HHCR on respiratory diseases in humans have not been well-studied. Therefore, we aimed to clarify the effectiveness of HHCR in patients with chronic bronchitis and bronchiectasis. METHODS: This was a multicenter (10 university teaching hospitals), open-label, prospective, single-arm, observational study. Consecutive patients with chronic bronchitis and bronchiectasis were included. Patients were orally treated with HHCR daily for 12 weeks. St. George's Respiratory Questionnaire (SGRQ) scores and bronchitis severity scores (BSS) were measured at baseline and at the end of the 12-week study. RESULTS: In total, 376 patients were enrolled, of which 304 were finally included in the study, including 236 males and 68 females with a median age of 69 years (range: 37-88 years). After 12 weeks of HHCR treatment, there was a significant improvement in SGRQ score (baseline, 32.52 ± 16.93 vs. end of study, 29.08 ± 15.16; p < 0.0001) and a significant reduction in BSS (baseline, 7.16 ± 2.63 vs. end of study, 4.72 ± 2.45; p < 0.0001). During the study, 14 patients concomitantly used an inhaled corticosteroid and 83 patients used an inhaled bronchodilator. HHCR also had significant positive effects on these patients in terms of SGRQ score and BSS. No serious adverse drug reactions occurred during HHCR treatment. CONCLUSIONS: treatment with HHCR improved the SGRQ score and BSS in patients with chronic bronchitis and bronchiectasis. HHCR may be a new therapeutic option for chronic bronchitis and bronchiectasis. Large-scale, randomized, double-blind, placebo-controlled clinical trials are warranted.

A Potential Quorum-Sensing Inhibitor for Bronchiectasis Therapy: Quercetin-Chitosan Nanoparticle Complex Exhibiting Superior Inhibition of Biofilm Formation and Swimming Motility of Pseudomonas aeruginosa to the Native Quercetin.

Quercetin (QUE)-a plant-derived flavonoid, is recently established as an effective quorum sensing (QS) inhibiting agent in Pseudomonas aeruginosa-the main bacterial pathogen in bronchiectasis lungs. Successful clinical application of QUE, however, is hindered by its low solubility in physiological fluids. Herein we developed a solubility enhancement strategy of QUE in the form of a stable amorphous nanoparticle complex (nanoplex) of QUE and chitosan (CHI), which was prepared by electrostatically driven complexation between ionized QUE molecules and oppositely charged CHI. At its optimal preparation condition, the QUE-CHI nanoplex exhibited a size of roughly 150 nm with a 25% QUE payload and 60% complexation efficiency. The complexation with CHI had no adverse effect on the antibacterial and anticancer activities of QUE, signifying the preservation of QUE's bioactivities in the nanoplex. Compared to the native QUE, the QUE-CHI nanoplex exhibited superior QS inhibition in suppressing the QS-regulated swimming motility and biofilm formation of P. aeruginosa, but not in suppressing the virulence factor production. The superior inhibitions of the biofilm formation and swimming motility afforded by the nanoplex were attributed to (1) its higher kinetic solubility (5-times higher) that led to higher QUE exposures, and (2) the synergistic QS inhibition attributed to its CHI fraction.

Managing Mycobacterium avium Complex Lung Disease With a Little Help From My Friend.

Management of Mycobacterium avium complex (MAC) lung disease is complicated, frequently unsuccessful, and frustrating to patients and clinicians. The initial treatment effort may not be directed solely at MAC infection, rather it is often initiating airway clearance measures for bronchiectasis. The next important steps are deciding who to treat and when to initiate therapy. Definitive or unambiguous guidance for these decisions is often elusive. The evidence supporting the current macrolide-based regimen for treating MAC lung disease is compelling. This regimen has been recommended in consensus nontuberculous mycobacterial treatment guidelines from 1997, 2007, and 2020, although clinician compliance with these recommendations is inconsistent. Understanding the idiosyncrasies of MAC antibiotic resistance is crucial for optimal antibiotic management. As a corollary, the importance of avoiding development of macrolide resistance due to inadequate therapy cannot be overstated. An inhaled liposome amikacin preparation is now approved for treating refractory MAC lung disease and holds promise for an even broader role in MAC therapy. Surgery is also an important therapeutic adjunct for selected patients. Microbiologic recurrences due either to new infection or treatment relapse/failure are common and require the same level of rigorous assessment and clinical judgment for determining their significance as initial MAC isolates. In summary, treatment of patients with MAC lung disease is rarely straight forward and requires familiarity with multiple factors directly and indirectly related to MAC lung disease. The many nuances of MAC lung disease therapy defy simple treatment algorithms; however, with patience, attention to detail, and perseverance, the outcome for most patients is favorable.