Concordance between Aspergillus-specific precipitating antibody and IgG in allergic bronchopulmonary aspergillosis

Abstracts: Background: Several serological tests for specific precipitin or IgG are available to demonstrate type III hypersensitivity reactions to Aspergillus species and are essential for infectious fungal disease diagnosis. These assays are also important for allergic bronchopulmonary aspergillosis (ABPA) diagnosis; however, their concordance in ABPA was not well studied. Methods: Fifty-two ABPA patients diagnosed based on ISHAM criteria were enrolled. Precipitins and IgG specific to Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, or Aspergillus terreus were measured using Ouchterlony double immunodiffusion tests and ImmunoCAP method, respectively. A. fumigatus-specific IgG was also determined using complement-fixation (CF) method. Results: Forty-eight percent of cases were double-positive for A. fumigatus-specific precipitin and IgG (ImmunoCAP), whereas 3 (6%) and 14 (28%) cases were positive for precipitin or IgG alone, respectively. Kappa coefficient between these measurements was 0.32, suggesting poor concordance. Double-positive cases were more likely to present: Aspergillus sp. in sputum culture, lower pulmonary functions, peripheral blood eosinophilia, higher total IgE and A. fumigatus-specific IgG titer than precipitin-negative cases. A. fumigatus-specific IgG (CF) was positive only in 8 (15%) cases. The presence of A. fumigatus-specific precipitin or IgG was associated with antibodies specific for other Aspergillus spp., suggesting cross-reactivity. Conclusions: Positive rate of A. fumigatus-specific precipitin or IgG (ImmunoCAP) was superior to IgG (CF), but relatively poor concordance was noted between precipitin and IgG (ImmunoCAP). Positive precipitin for A. fumigatus suggests more active diseases. Cross-reactivity may exist between antibodies to different Aspergillus spp. Therefore, the type III hypersensitivity results in ABPA diagnosis should be carefully evaluated. Keywords: ABPA, Aspergillus fumigatus, concordance, IgG, precipiti

Proportion and clinical characteristics of non-asthmatic non-smokers among adults with airflow obstruction

<div><p>Background and objectives</p><p>Chronic obstructive pulmonary disease (COPD) mainly develops after long-term exposure to cigarette or biomass fuel smoke, but also occurs in non-smokers with or without a history of asthma. We investigated the proportion and clinical characteristics of non-smokers among middle-aged to elderly subjects with airflow obstruction.</p><p>Methods</p><p>We retrospectively analyzed 1,892 subjects aged 40–89 years who underwent routine preoperative spirometry at a tertiary university hospital in Japan. Airflow obstruction was defined as a forced expiratory volume in 1 second (FEV₁)/forced vital capacity < 0.7 or as the lower limit of the normal.</p><p>Results</p><p>Among 323 patients presenting with FEV₁/forced vital capacity < 0.7, 43 had asthma and 280 did not. Among the non-asthmatic patients with airflow obstruction, 94 (34%) were non-smokers. A larger number of women than men with airflow obstruction had asthma (26% vs. 7.6%, p < 0.001), or were non-smokers among non-asthmatics (72% vs. 20%, p < 0.001). Non-asthmatic non-smokers, rather than non-asthmatic smokers, asthmatic non-smokers, and asthmatic smokers, exhibited better pulmonary function (median FEV₁: 79% of predicted FEV₁ vs. 73%, 69%, and 66%, respectively, p = 0.005) and less dyspnea on exertion (1% vs. 12%, 12%, and 28%, respectively, p = 0.001). Pulmonary emphysema on thoracic computed tomography was less common in non-smokers (p < 0.001). Using the lower limit of the normal to define airflow obstruction yielded similar results.</p><p>Conclusions</p><p>There are a substantial number of non-smokers with airflow obstruction compatible with COPD in Japan. In this study, airflow obstruction in non-smokers was more common in women and likelier to result in mild functional and pathological abnormalities than in smokers. Further studies are warranted to investigate the long-term prognosis and appropriate management of this population in developed countries, especially in women.</p></div

Box-and-whisker plot of the median FEV₁ (% predicted) in patients with airflow obstruction.

<p>The median FEV₁ (% predicted) was stratified by the presence or absence of a history of smoking and self-reported asthma. * p < 0.05.</p

Clinical characteristics according to smoking habits and history of asthma among patients with airflow obstruction, as defined by FEV₁/FVC < 0.7.

<p>Clinical characteristics according to smoking habits and history of asthma among patients with airflow obstruction, as defined by FEV₁/FVC < 0.7.</p

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

Proportions of non-smokers and smokers with or without self-reported asthma among patients with airflow obstruction.

<p>Proportions of non-asthmatic non-smokers, non-asthmatic smokers, asthmatic non-smokers, and asthmatic smokers among patients with airflow obstruction are shown according to age group in men (A and B) and women (C and D). Airflow obstruction was defined as FEV₁/FVC < 0.70 (A and C) or FEV₁/FVC < LLN (B and D).</p

Clinical contributions of exhaled volatile organic compounds in the diagnosis of lung cancer

<div><p>Background</p><p>Exhaled volatile organic compounds (VOC) are being considered as biomarkers for various lungs diseases, including cancer. However, the accurate measurement of extremely low concentrations of VOC in expired air is technically challenging. We evaluated the clinical contribution of exhaled VOC measured with a new, double cold-trap method in the diagnosis of lung cancer.</p><p>Methods</p><p>Breath samples were collected from 116 patients with histologically confirmed lung cancer and 37 healthy volunteers (controls) after inspiration of purified air, synthesized through a cold-trap system. The exhaled VOC, trapped in the same system, were heat extracted. We analyzed 14 VOC with gas chromatography.</p><p>Results</p><p>The concentrations of exhaled cyclohexane and xylene were significantly higher in patients with lung cancer than in controls (<i>p</i> = 0.002 and 0.0001, respectively), increased significantly with the progression of the clinical stage of cancer (both <i>p</i> < 0.001), and decreased significantly after successful treatment of 6 patients with small cell lung cancer (p = 0.06 and 0.03, respectively).</p><p>Conclusion</p><p>Measurements of exhaled VOCs by a double cold-trap method may help diagnose lung cancer and monitor its progression and regression.</p></div

Comparison between exhaled cyclohexane (A) and xylene (B) in 6 patients with small cell lung cancer before treatment and after response to therapy.

<p>*<i>p</i> < 0.05 versus before treatment.</p