Type 2 Biomarkers and Their Clinical Implications in Bronchiectasis: A Prospective Cohort Study.

PURPOSE: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. METHODS: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. RESULTS: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/µL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. CONCLUSIONS: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

Increasing serum miR-223-3p indicates the onset, severe development, and adverse prognosis of bronchiectasis: a retrospective study.

BACKGROUND: miR-223-3p has been demonstrated as a Pseudomonas aeruginosa colonization-related miRNA in bronchiectasis (BE), but its clinical value in BE has not been revealed, which is of great significance for the clinical diagnosis and monitoring of BE. This study aimed to identify a reliable biomarker for screening BE and predicting patients' outcomes. METHODS: The serum expression of miR-223-3p was compared between healthy individuals (n = 101) and BE patients (n = 133) and evaluated its potential in distinguishing BE patients. The severity of BE patients was estimated by BSI and FACED score, and the correlation of miR-223-3p with inflammation and severity of BE patients was evaluated by Pearson correlation analysis. BE patients were followed up for 3 years, and the predictive value of miR-223-3p in prognosis was assessed by logistic regression analysis. RESULTS: Significant upregulation of miR-223-3p was observed in BE patients, which significantly distinguished BE patients and showed positive correlations with C-reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL-6), and neutrophil-to-lymphocyte ratio (NLR) of BE patients. Additionally, miR-223-3p was also positively correlated with BSI and FACED scores, indicating its correlation with inflammation and severity of BE. BE patients with adverse prognoses showed a higher serum miR-223-3p level, which was identified as an adverse prognostic factor and discriminated patients with different prognoses. CONCLUSION: Increasing serum miR-223-3p can be considered a biomarker for the onset, severity, and prognosis of BE.

Pulmonary Follow-Up Imaging in Cartilage-Hair Hypoplasia: a Prospective Cohort Study.

Cartilage-hair hypoplasia is a syndromic immunodeficiency with short stature, chondrodysplasia, and variable degree of immune dysfunction. Patients with cartilage-hair hypoplasia are prone to recurrent respiratory tract infections, and the prevalence of bronchiectasis ranges from 29 to 52%. Pulmonary complications contribute significantly to the mortality; therefore, regular lung imaging is essential. However, the optimal schedule for repeated lung imaging remains unestablished. We determined the rate and correlates of progression of structural lung changes in a prospectively followed cohort of 16 patients with cartilage-hair hypoplasia. We analyzed clinical, laboratory, and pulmonary functional testing data and performed lung magnetic resonance imaging at a median interval of 6.8 years since previous imaging. Imaging findings remained identical or improved due to disappearance of inflammatory changes in all evaluated patients. Patients with subtle signs of bronchiectasis on imaging tended to have low immunoglobulin M levels, as well as suffered from pneumonia during the follow-up. In conclusion, our results suggest slow if any development of bronchiectasis in selected subjects with cartilage-hair hypoplasia.

Serum Krebs von den Lungen-6 level in the disease progression and treatment of Mycobacterium avium complex lung disease.

BACKGROUND AND OBJECTIVE: The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC-LD). We clarified the associations between serum KL-6 level, disease progression and treatment response. METHODS: Resected lung tissues from MAC-LD patients were immunostained for KL-6. We compared serum KL-6 levels between MAC-LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM-LD). Serum KL-6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL-6 level and disease progression and treatment response in patients untreated for MAC-LD on registration (n = 187). RESULTS: The KL-6+ alveolar type 2 cell population in the lung and serum KL-6 level were significantly higher in MAC-LD patients than in controls. Serum KL-6 level in bronchiectasis patients without NTM-LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL-6 level (aHR: 1.18, P = 0.005), positive acid-fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL-6 (ΔKL-6) was significantly higher in the disease progression group; it decreased post-treatment, reflecting the negative sputum culture conversion. CONCLUSION: Serum KL-6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC-LD management.

Sensitization to A fumigatus in subjects with non-cystic fibrosis bronchiectasis.

BACKGROUND: Patients with chronic lung diseases, including cystic fibrosis (CF), are frequently sensitized to Aspergillus fumigatus. Whether patients with non-CF bronchiectasis develop sensitization to A fumigatus remains unknown. OBJECTIVE: To evaluate the prevalence of sensitization and chronic infection with A fumigatus in subjects with bronchiectasis. We also performed a multivariate logistic regression analysis to identify factors predicting sensitization and chronic A fumigatus infection. METHODS: Subjects with bronchiectasis were investigated with serum A fumigatus-specific IgE and IgG, and sputum cultures for bacteria, fungus and mycobacteria. We defined A fumigatus sensitization and chronic A fumigatus infection as serum A fumigatus-specific IgE and IgG > 0.35 kUA/L and >27 mgA/L, respectively. We excluded subjects with bronchiectasis secondary to allergic bronchopulmonary aspergillosis. RESULTS: We included 258 subjects (TB [n = 155], idiopathic [n = 66] and other causes [n = 37]) with bronchiectasis. The prevalence of Aspergillus sensitization, chronic Aspergillus infection, and both sensitization and chronic infection was 29.5% (76/258), 76% (196/258) and 26% (68/258), respectively. In a multivariate logistic regression analysis, TB-related bronchiectasis was an independent risk factor for Aspergillus sensitization. Chronic Aspergillus infection was predicted by the duration of symptoms and specific aetiologies (tuberculosis and idiopathic) of bronchiectasis. The growth of Aspergillus species was also frequent in the TB group compared with other causes (32% vs 2%; P < .001). CONCLUSIONS: We found a significant occurrence of Aspergillus sensitization and chronic infection in non-CF bronchiectasis, especially in TB bronchiectasis. In addition to Aspergillus sensitization, investigations for chronic Aspergillus infection should be routinely performed in non-CF bronchiectasis, both at diagnosis and during follow-up.

The association between serum albumin/prealbumin level and disease severity in non-CF bronchiectasis.

Non-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disease that can lead to malnutrition. Serum prealbumin and albumin level are related to inflammatory and nutritional status. Thus, we aimed to confirm our hypothesis that low serum albumin and prealbumin level, as well as body mass index (BMI), is correlated to severe non-CF bronchiectasis. We conducted a retrospective cross-sectional study of 128 patients, including 75 patients with prealbumin test and 79 patients with albumin test. Detailed medical history was recorded, including pulmonary function tests and high-resolution computed tomography. bronchiectasis severity index (BSI) and FACED scores were calculated. Leicester Cough Questionnaire, Quality of Life Questionnaire-Bronchiectasis, chronic obstructive pulmonary disease (COPD) assessment test and Patient Health Questionnaire-9 questionnaires were used to assess patients' clinical symptoms. Correlation analysis showed that BSI score was more correlated to patients' clinical symptoms than FACED. Thus, patients were divided into three groups of different severity based on BSI score. Albumin, prealbumin and BMI showed a significant difference between three groups. Correlation and multivariable linear regression analysis showed that serum albumin and prealbumin level were correlated to BSI, FACED and questionnaires. The analysis between three indices and PFT/high-resolution computed tomography (HRCT) showed that prealbumin, albumin and BMI could reflect the PFT and modified Reiff score in non-CF bronchiectasis. In conclusion, BMI, albumin and prealbumin showed a significant correlation with the BSI, FACED, as well as patients' clinical symptoms. Among them, serum albumin was the indicator most strongly associated with the BSI and questionnaires, while prealbumin could better reflect lung function decline and radiological severity.

Clinical and immunological features of 44 common variable immunodeficiency patients: the experience of a single center in Turkey.

INTRODUCTION AND OBJECTIVES: Common variable immunodeficiency (CVID) is one of the most prevalent forms of primary immunodeficiency characterized by hypogammaglobinemia. Its heterogeneous clinical features include recurrent respiratory tract infections and other complications such as gastrointestinal, autoimmunity, and lymphoproliferative disorders. The aim of this article is to evaluate the general characteristics of CVID patients. MATERIALS AND METHODS: Clinical and immunological features of 44 CVID patients were evaluated retrospectively with long-term follow-up. Patients who participated in the study were diagnosed according to the criteria of the European Society for Immunodeficiency Diseases (ESID). RESULTS: The median age at onset of symptoms was 2.75 years (range 6 months to 17 years), and the median age at diagnosis was 7.75 years (range 4-20 years). The average delay in diagnosis was 4.6 years (range 1-14 years). Positive family history was 18.2%. Before treatment, patients' median total serum IgG was 271.5mg/dL, median IgA was 7.5mg/dL, and median IgM was 21mg/dL. Infections were the most common clinical manifestation, and 63.6% of patients presented with sinopulmonary infection as the first manifestation. Bronchiectasis developed in 23 CVID subjects, while bronchiectasis was detected prior to CVID diagnosis in eight patients. All patients received immunoglobulin replacement therapy, and one patient died because of granulomatous lymphocytic interstitial lung disease (GLILD). CONCLUSIONS: CVID is a heterogeneous group of immunologic disorders with unknown etiology. There are significant differences in the clinical presentation and prevalence of CVID-related complications among countries. Local guidelines for diagnosis and clinical follow-up are needed.

Low serum estradiol levels are related to Mycobacterium avium complex lung disease: a cross-sectional study.

BACKGROUND: The risk factors for Mycobacterium avium complex lung disease (MAC-LD) are not well known. We hypothesized that low serum estradiol (E2) levels are related to MAC-LD as most patients with MAC-LD are postmenopausal women. METHODS: This cross-sectional study compared patients with MAC-LD and healthy controls. Study subjects were postmenopausal women aged 65 years or younger. Serum testosterone, dehydroepiandrosterone sulfate (DHEA-S), and E2 levels were measured and categorized as high or low based on median levels. We performed multivariate analysis, receiver operating characteristic (ROC) curve analysis, and age- and body mass index (BMI)-matched subgroup analysis to evaluate the association between low serum E2 levels and MAC-LD. Additionally, using blood samples obtained for other clinical studies, the levels of sex steroid hormones were compared between age- and BMI-matched MAC-LD and bronchiectasis female patients without non-tuberculosis mycobacterial infections (non-NTM BE). RESULTS: Forty-two patients with MAC-LD and 91 healthy controls were included. The median E2 (2.20 pg/mL vs. 15.0 pg/mL, p < 0.001), testosterone (0.230 ng/L vs. 0.250 ng/L, p = 0.005), and DHEA-S (82.5 µg/dL vs. 114.0 µg/dL, p < 0.001) levels were lower in the MAC-LD group than in the control group. Multivariate analysis revealed that low serum E2 (adjusted odds ratio = 34.62, 95% confidence interval = 6.02-199.14) was independently related to MAC-LD, whereas low DHEA-S and testosterone were not. ROC analysis illustrated a strong relationship between low serum E2 levels and MAC-LD (area under the curve = 0.947, 95% confidence interval = 0.899-0.995). Even the age- and BMI-matched subgroup analysis of 17 MAC-LD patients and 17 healthy controls showed lower serum E2 in MAC-LD patients than in healthy controls. Additionally, serum E2 levels of 20 MAC-LD patients were lower than plasma E2 levels of 11 matched non-NTM BE patients (1.79 pg/mL vs. 11.0 pg/mL, p < 0.001). CONCLUSIONS: Low serum E2 levels were strongly related to MAC-LD in postmenopausal women.

Blood Neutrophils Are Reprogrammed in Bronchiectasis.

RATIONALE: Excessive neutrophilic airway inflammation is the central feature of bronchiectasis, but little is known about neutrophils in bronchiectasis. OBJECTIVES: To assess blood neutrophil phenotype in patients with bronchiectasis while stable and during exacerbations. METHODS: In the clinically stable arm of this study, there were eight healthy volunteers, eight patients with mild bronchiectasis, and eight patients with severe bronchiectasis. In addition, six patients with severe bronchiectasis were compared with six patients with community-acquired pneumonia at the start and end of an exacerbation. We assessed neutrophils for spontaneous apoptosis, cell surface marker expression, degranulation, reactive oxygen species generation, phagocytosis, and killing of Pseudomonas aeruginosa (PAO1). In addition, blood neutrophil function was compared with airway neutrophil function in bronchiectasis. MEASUREMENTS AND MAIN RESULTS: In stable bronchiectasis, compared with healthy volunteers, blood neutrophils had significantly prolonged viability, delayed apoptosis, increased CD62L shedding, upregulated CD11b expression, increased myeloperoxidase release, and impaired neutrophil phagocytosis and killing of PAO1. Bronchiectatic airway neutrophils had significantly lower bacterial phagocytosis and killing than their matched autologous blood neutrophils. Both blood and airway neutrophil phagocytosis and killing were impaired at the start of an exacerbation and improved following antibiotic treatment. In pneumonia, there was a significant improvement in phagocytosis and killing after treatment with antibiotics. During infections, there was no difference in phagocytosis, but there was significantly increased bacterial killing at the start and end of infection in pneumonia compared with bronchiectasis exacerbations. CONCLUSIONS: In bronchiectasis stable state, peripheral blood neutrophils are reprogrammed and have prolonged survival. This impairs their functional ability of bacterial phagocytosis and killing, thereby perpetuating the vicious circle in bronchiectasis.

[Respiratory pathogen spectrum in pulmonary exacerbation of bronchiectasis in adults and its association with disease severity].

Objective: To determine the pattern of respiratory pathogens at bronchiectasis exacerbation and its associations with disease severity. Methods: A total of 119 steady-state bronchiectasis patients [42 males, 77 females, age range 19 to 74 years, mean age (45±14)years], diagnosed by a compatible history combined with evidence of bronchial dilatation on high-resolution computed tomography (HRCT), were recruited prospectively from out-patient clinics in the First Affiliated Hospital of Guangzhou Medical University between September 2012 and March 2013. A comprehensive history taking, radiologic appearance, spirometry, sputum bacterial culture and 16 respiratory viruses in nasopharyngeal swabs and sputum samples by PCR assays were collected at steady-state bronchiectasis. All bronchiectasis patients were followed up one year and assessed for bacteriology, virology and systemic inflammatory indices [including white blood cell, C-reactive protein (CRP), interleukin-6, 8 and tumor necrosis factor-α] during bronchiectasis exacerbation. Results: Fifty-eight bronchiectasis patients [20 males, 38 females, age range 19 to 74 years, mean age (44±14) years] reported 100 exacerbations (1 to 5 exacerbation events per patient) during one year follow-up. Respiratory viruses were found more frequently in sputum and nasal swab during exacerbation [35.0% (35/100) and 39% (39/100)] than those during steady-state in bronchiectasis [sputum: 13.8% (8/58), nasal swab: 8.6% (5/58)] (χ(2)=8.33,χ(2)=13.51; respectively, all P<0.05). The rate of bacterial detection during exacerbation in sputum was 56% (56/100), which was not significantly different compared with those at steady-state (35/58, 60.3%;χ(2)=0.284, P=0.59). Of these respiratory infections, viral-bacterial co-infection accounted for 30% exacerbation events. The most common bacteria and viruses during exacerbation in mild bronchiectasis (n=18, with 25 exacerbation events) were Haemophilus parainfluenzae (4 cases) in sputum and influenza A in nasal swab or sputum (4 cases), respectively. In patients with moderate (n=17, with 29 exacerbation events)-severe bronchiectasis (n=23, with 46 exacerbation events), pseudomonas aeruginosa was the most common bacteria in sputum (35 cases), and the most common respiratory viruses were rhinovirus in nasal swab or sputum (11 cases). In these 100 exacerbation events, patients with bacterial and viral co-infection, pure bacteria infection, pure virus infection, no bacteria and virus infection accounted for 30, 29, 16 and 25 exacerbation events, respectively. And patients with co-infection had higher serum CRP (45±23) mg/L and IL-8 [9.0 (4.4-15.5) ng/L] (F=23.32, F=9.81,respectively; all P<0.05), and increased risk of hospitalization (30% vs. 0] compared with those in non-infectious group(χ(2)=9.0, P=0.003). Conclusions: Pseudomonas aeruginosa, rhinovirus and influenza A were common causative agents of exacerbation in bronchiectasis.In patients with moderate-severe bronchiectasis, pseudomonas aeruginosa was the most common bacterium in sputum, and the most common respiratory virus was rhinovirus in nasal swab or sputum, compared to Haemophilus parainfluenzae in sputum and influenza A in nasal swab or sputum in mild bronchiectasis. Patients with co-infection had more severe systemic inflammatory response and higher risk of hospitalization during exacerbation.

Characteristics of patients with bronchoscopy-diagnosed pulmonary Mycobacterium avium complex infection.

BACKGROUND: We occasionally treat patients with clinically suspected pulmonary Mycobacterium avium complex (MAC) infection and negative MAC culture on bronchoscopy. OBJECTIVE: This study aimed to investigate the usefulness of bronchoscopy in patients with suspected MAC lung disease with nodular bronchiectasis on chest computed tomography (CT) and to clarify the clinical characteristics of these patients. METHODS: We reviewed the records of 71 patients with clinically suspected pulmonary MAC infection on chest CT who underwent bronchoscopy. The patients were classified on the basis of MAC culture result, and their clinical characteristics were compared. RESULTS: MAC was detected in 33 of the 71 (46.5%) patients (positive group), and 35 (49.3%) were culture-negative for nontuberculous mycobacteria (NTM) (negative group). NTM other than MAC were detected in 3 of 71 (4.2%) patients. MAC was not detected in 14 of 38 (36.8%) patients positive for GPL core IgA antibody. Patients in the positive group had a higher body mass index (20.1 ± 3.4 vs 18.5 ± 2.9 kg/m2; p = 0.047) and positive rate for GPL core IgA antibody (72.7% vs 40%; p = 0.006) and a lower chronic obstructive pulmonary disease assessment test score (6.6 ± 6.6 vs 11.7 ± 8.5; p = 0.016) and rate of positive culture for Pseudomonas aeruginosa or Haemophilus influenzae (12.1% vs 45.7%; p = 0.003), as compared with the negative group. CONCLUSION: Bronchoscopy is useful for diagnosis of MAC in patients who cannot be diagnosed by sputum examination. In addition, patients with pulmonary MAC disease had less severe subjective symptoms and weight loss than did those with a negative MAC culture on bronchoscopy.

Vitamin D levels in asthmatic patients with and without allergic bronchopulmonary aspergillosis.

Vitamin D deficiency is believed to be a pathogenetic factor in patients with allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. Whether vitamin D deficiency is also prevalent in ABPA complicating asthma, remains unknown. Herein, we evaluated vitamin D levels in asthmatic patients with and without ABPA. In a prospective study, plasma vitamin D (25[OH]D) levels were measured in consecutive subjects with asthma (n = 75), ABPA (n = 158) and healthy volunteers (n = 50). Vitamin D levels <20 ng/mL were considered as vitamin D deficiency. There was no difference in mean (95% CI) vitamin D levels between healthy controls (15.3 [12.7-17.9]), asthmatics (19.2 [16.3-22.1]) and subjects with ABPA (18.9 [16.9-20.8]) (P = .22). Vitamin D deficiency was encountered in 70%, 64% and 65% of the healthy controls, asthmatics and ABPA subjects, respectively, and was not different between the groups (P = .79). There was no difference in the asthma control, pulmonary function, immunological findings and the severity of bronchiectasis, in patients with ABPA, with and without vitamin D deficiency. Vitamin D deficiency is equally prevalent in asthmatic patients with or without ABPA in the Indian subcontinent, and does not appear to play a major role in the pathogenesis of ABPA complicating asthma.

Vitamin D3 supplementation in adults with bronchiectasis: A pilot study.

Vitamin D supplementation prevents acute respiratory infections and, through modulating innate and adaptive immunity, could have a potential role in bronchiectasis management. The primary aims of this pilot study were to assess serum 25-hydroxyvitamin D (25(OH)D) levels in New Zealand adults with bronchiectasis, and their 25(OH)D levels after vitamin D3 supplementation. Adults with bronchiectasis received an initial 2.5 mg vitamin D3 oral loading dose and 0.625 mg vitamin D3 weekly for 24 weeks. The primary outcome was serum 25(OH)D levels before and after vitamin D3 supplementation. Secondary outcomes (time to first infective exacerbation, exacerbation frequency, spirometry, health-related quality of life measures, sputum bacteriology and cell counts and chronic rhinosinusitis) were also assessed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12612001222831). The initial, average 25(OH)D level was 71 nmol/L (95% confidence interval (CI): [58, 84]), rising to 218 nmol/L (95% CI: [199, 237]) at 12 weeks and 205 nmol/L (95% CI: [186, 224]) at 24 weeks. The initial serum cathelicidin level was 25 nmol/L (95% CI: [17, 33]), rising to 102 nmol/L (95% CI: [48, 156]) at 12 weeks and 151 nmol/L (95% CI: [97, 205]) at 24 weeks. Over the 24-week study period, we observed statistically significant changes of 1.11 (95% CI: [0.08, 2.14]) in the Leicester Cough Questionnaire and -1.97 (95% CI: [-3.71, -0.23]) in the Dartmouth COOP charts score. No significant adverse effects were recorded. Many New Zealand adults with bronchiectasis have adequate 25(OH)D levels. Weekly vitamin D3 supplementation significantly improved 25(OH)D levels.

Allergic bronchopulmonary aspergillosis in Japan: A nationwide survey.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease characterized by a hypersensitivity reaction to Aspergillus species colonizing the airways. The clinical characteristics of ABPA may differ depending on genetic and environmental background. We performed a nationwide survey to determine the clinical characteristics of ABPA in Japan. METHODS: In 2013, a questionnaire on physician-diagnosed ABPA/allergic bronchopulmonary mycosis was sent to 903 medical centers specializing in respiratory or allergic diseases. Cases fulfilling the following criteria were categorized as possible ABPA-central bronchiectasis (ABPA-CB): 1) presence of specific serum immunoglobulin E (IgE) antibodies or a positive skin reaction to Aspergillus, and 2) bronchiectasis or mucoid impaction in the central bronchi. RESULTS: Of 499 physician-diagnosed cases reported by 132 clinical centers, 358 cases met the criteria for possible ABPA-CB. Median age of ABPA-CB onset was 57 (interquartile range, 44-68) years; later-onset disease, developing ≥50 years of age, accounted for 66% of the cases and was associated with female sex, delayed onset of asthma, and lower levels of serum IgE. A third of the patients (120 patients, 34%) exhibited low levels of serum total IgE (<1000 IU/mL). Aspergillus species were isolated from sputum in 126/213 cases (59%), and Schizophyllum commune was identified in 12 (6%) patients. During the course of the treatment, ABPA recurred in 169 (48%) cases. CONCLUSIONS: This nationwide survey identified several unique clinical characteristics of ABPA in Japan, such as late-onset, relatively lower serum IgE levels, and frequent recurrences/flares.

A New SERPINA-1 Missense Mutation Associated with Alpha-1 Antitrypsin Deficiency and Bronchiectasis.

Alpha-1-antitrypsin deficiency (AATD) is a genetic condition caused by SERPINA1 mutations, which culminates into lower protease inhibitor activity in the serum and predisposes to emphysema. Clinical manifestations of AATD are often associated to ZZ (p.Glu342Lys) and SZ (p.Glu264Val) genotypes and less frequently to rare deficiency or null alleles in heterozygous and homozygous states. We report a case of a 52-year-old woman with bronchiectasis without other potential causes other than an electrophoresis that showed a decrease of alpha-1 globin band and AAT levels below the normal value (78 mg/dl; v.n. 90-200 mg/dl). No S or Z mutation was identified, but sequencing analysis found a novel missense variant Ile74Asn (c.221T > A) in heterozygous state on an M3 allele (Glu400Asp) in the exon 2 of the SERPINA-1gene, probably leading to a dysfunctional protein. This mutation has never been previously identified, and it is interesting to note the association with bronchiectasis in the absence of emphysema.

[Study on the effect and predictive to bronchiectasis combined with rheumatoid arthritis].

Objective: To explore the clinical characteristics of bronchiectasis(BR)coexisting in patients with rheumatoid arthritis (RA). Methods: One hundred and forty-eight bronchiectasis patients were retrospectively analyzed. These cases were all diagnosed in the Respiratory Department of Shanghai Pulmonary Hospital and Shanghai Gongli Hospital of Pudong New Area during Jan. 2012 to Dec.2015.The patients consisted of 74 males and 74 females, aging from 45 to 79 [mean(65±11)] years. In these patients, coexisting rheumatoid arthritis was found in 34 males and 36 females, aging from 45 to 79[mean(68±12)] years(RA-BR group). Patients with bronchiectasis alone consisted of 40 males and 38 females, aging from 49 to 76 [mean(63±10)] years (BR alone group). Data between the 2 groups of patients were compared, including general clinical features, serum anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), chest high-resolution CT (HRCT), and lung function . FACED scores were used to assess the severity of bronchiectasis. Meanwhile, we analyzed the correlation between anti-CCP and FACED scores in the 2 groups. Results: We observed an increase of serum anti-CCP in RA-BR patients compared with BR alone patients (196±68 versus 64±26, P<0.05). In addition, FACED scores in RA-BR patients were higher than those in BR patients (5.2±1.8 versus 3.1±1.4 , P< 0.05). Positive correlations between serum anti-CCP levels and FACED scores (r=0.678, r=0.461, P<0.05) in both RA-BR and BR alone groups were observed in this study. Conclusions: The disease severity scores of RA-BR patients were higher than those of patients with BR alone. Levels of serum anti-CCP may act as a predictor for the diagnosis and prognosis of bronchiectasis in patients with RA.

Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency.

Polysaccharide antibody deficiency is characterized by a poor or absent antibody response after vaccination with an unconjugated pneumococcal polysaccharide vaccine. Allohaemagglutinins (AHA) are antibodies to A or B polysaccharide antigens on the red blood cells, and are often used as an additional or alternative measure to assess the polysaccharide antibody response. However, few studies have been conducted to establish the clinical significance of AHA. To investigate the value of AHA to diagnose a polysaccharide antibody deficiency, pneumococcal polysaccharide antibody titres and AHA were studied retrospectively in 180 subjects in whom both tests had been performed. Receiver operating characteristic curves for AHA versus the pneumococcal vaccine response as a marker for the anti-polysaccharide immune response revealed an area under the curve between 0·5 and 0·573. Sensitivity and specificity of AHA to detect a polysaccharide antibody deficiency, as diagnosed by vaccination response, were low (calculated for cut-off 1/4-1/32). In subjects with only low pneumococcal antibody response, the prevalence of bronchiectasis was significantly higher than in subjects with only low AHA (45·5 and 1·3%, respectively) or normal pneumococcal antibody response and AHA (2·4%). A logistic regression model showed that low pneumococcal antibody response but not AHA was associated with bronchiectasis (odds ratio 46·2). The results of this study do not support the routine use of AHA to assess the polysaccharide antibody response in patients with suspected immunodeficiency, but more studies are warranted to clarify the subject further.

Low ficolin-2 levels in common variable immunodeficiency patients with bronchiectasis.

Common variable immunodeficiency (CVID) encompasses a heterogeneous group of antibody deficiencies characterized by susceptibility to recurrent infections and sequelae, including bronchiectasis. We investigated the relevance of the lectin complement pathway in CVID patients by analysing ficolin-2 and ficolin-3 serum levels and genotyping single nucleotide polymorphisms (SNPs) in the FCN2 and FCN3 genes. Our results show that ficolin-2 levels in CVID patients are significantly lower (P < 0.0001) than in controls. The lowest ficolin-2 levels are found in CVID patients with bronchiectasis (P = 0.0004) and autoimmunity (P = 0.04). Although serum levels of ficolin-3 were similar in CVID patients and controls, CVID patients with bronchiectasis again showed lower levels when compared to controls (P = 0.0001). Analysis of single nucleotide polymorphisms in the FCN2 gene confirmed known influences on ficolin-2 serum levels, but did not support a genetic basis for the observed ficolin-2 deficiency in CVID. We found that CVID patients with bronchiectasis have very low levels of ficolin-2. The reason for the deficiency of ficolin-2 in CVID and any possible causal relationship is currently unknown. However, as bronchiectasis is a very important factor for morbidity and mortality in CVID, ficolin-2 could also serve as biomarker for monitoring disease complications such as bronchiectasis.

Lung function, symptoms and inflammation during exacerbations of non-cystic fibrosis bronchiectasis: a prospective observational cohort study.

BACKGROUND: Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described. METHODS: This was a prospective observational cohort study of 32 outpatients with non-cystic fibrosis bronchiectasis conducted between August 2010 and August 2012. Patients completed a symptom diary card and measured their peak expiratory flow rate (PEFR) daily. Exacerbations were defined as oral antibiotic treatment taken for a worsening of respiratory symptoms. Symptoms and peak flow at exacerbation were analysed, and further measurements including the COPD Assessment Test (CAT) and inflammatory markers were also compared to baseline values. RESULTS: At baseline, health status was significantly related to lung function, prognostic severity and systemic inflammation. 51 exacerbations occurred in 22 patients. Exacerbation symptoms began a median (interquartile range) of 4 (2, 7) days before treatment started and the median exacerbation duration was 16 (10, 29) days. 16% had not recovered by 35 days. At exacerbation, mean PEFR dropped by 10.6% (95% confidence interval 6.9-14.2, p < 0.001) and mean CAT score increased by 6.3 units (3.6-9.1, p = 0.001), median symptom count by 4 (2.25, 6, p < 0.001), and mean CRP by 9.0mg/L (2.3-15.8, p = 0.011). Exacerbations where PEFR fell by ≥10% were longer with more symptoms at onset. CONCLUSION: Exacerbations of non-CF bronchiectasis are inflammatory events, with worsened symptoms, lung function and health status, and a prolonged recovery period. Symptom diary cards, PEFR and CAT scores are responsive to changes at exacerbation and may be useful tools for their detection and monitoring.