Increased Chitotriosidase Is Associated With Aspergillus and Frequent Exacerbations in South-East Asian Patients With Bronchiectasis.

BACKGROUND: Chitinase activity is an important innate immune defence mechanism against infection that includes fungi. The 2 human chitinases: chitotriosidase (CHIT1) and acidic mammalian chitinase are associated to allergy, asthma, and COPD; however, their role in bronchiectasis and bronchiectasis-COPD overlap (BCO) is unknown. RESEARCH QUESTION: What is the association between chitinase activity, airway fungi and clinical outcomes in bronchiectasis and bronchiectasis-COPD overlap? STUDY DESIGN AND METHODS: A prospective cohort of 463 individuals were recruited across five hospital sites in three countries (Singapore, Malaysia, and Scotland) including individuals who were not diseased (n = 35) and who had severe asthma (n = 54), COPD (n = 90), bronchiectasis (n = 241) and BCO (n = 43). Systemic chitinase levels were assessed for bronchiectasis and BCO and related to clinical outcomes, airway Aspergillus status, and underlying pulmonary mycobiome profiles. RESULTS: Systemic chitinase activity is elevated significantly in bronchiectasis and BCO and exceed the activity in other airway diseases. CHIT1 activity strongly predicts bronchiectasis exacerbations and is associated with the presence of at least one Aspergillus species in the airway and frequent exacerbations (≥3 exacerbations/y). Subgroup analysis reveals an association between CHIT1 activity and the "frequent exacerbator" phenotype in South-East Asian patients whose airway mycobiome profiles indicate the presence of novel fungal taxa that include Macroventuria, Curvularia and Sarocladium. These taxa, enriched in frequently exacerbating South-East Asian patients with high CHIT1 may have potential roles in bronchiectasis exacerbations. INTERPRETATION: Systemic CHIT1 activity may represent a useful clinical tool for the identification of fungal-driven "frequent exacerbators" with bronchiectasis in South-East Asian populations.

A clinical prediction model for hospitalized COPD exacerbations based on "treatable traits".

Background: Assessing risk of future exacerbations is an important component in COPD management. History of exacerbation is a strong and independent predictor of future exacerbations, and the criterion of ≥2 nonhospitalized or ≥1 hospitalized exacerbation is often used to identify high-risk patients in whom therapy should be intensified. However, other factors or "treatable traits" also contribute to risk of exacerbation. Objective: The objective of the study was to develop and externally validate a novel clinical prediction model for risk of hospitalized COPD exacerbations based on both exacerbation history and treatable traits. Patients and methods: A total of 237 patients from the COPD Registry of Changi General Hospital, Singapore, aged 75±9 years and with mean post-bronchodilator FEV1 60%±20% predicted, formed the derivation cohort. Hospitalized exacerbation rate was modeled using zero-inflated negative binomial regression. Calibration was assessed by graphically comparing the agreement between predicted and observed annual hospitalized exacerbation rates. Predictive (discriminative) accuracy of the model for identifying high-risk patients (defined as experiencing ≥1 hospitalized exacerbations) was assessed with area under the curve (AUC) and receiver operating characteristics analyses, and compared to other existing risk indices. We externally validated the prediction model using a multicenter dataset comprising 419 COPD patients. Results: The final model included hospitalized exacerbation rate in the previous year, history of acute invasive/noninvasive ventilation, coronary artery disease, bronchiectasis, and sputum nontuberculous mycobacteria isolation. There was excellent agreement between predicted and observed annual hospitalized exacerbation rates. AUC was 0.789 indicating good discriminative accuracy, and was significantly higher than the AUC of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) risk assessment criterion (history of ≥1 hospitalized exacerbation in the previous year) and the age, dyspnea, and obstruction index. When applied to the independent multicenter validation cohort, the model was well-calibrated and discrimination was good. Conclusion: We have derived and externally validated a novel risk prediction model for COPD hospitalizations which outperforms several other risk indices. Our model incorporates several treatable traits which can be targeted for intervention to reduce risk of future hospitalized exacerbations.

EUS-FNA of the left adrenal gland is safe and useful.

INTRODUCTION: There are limited data on the use of endosonography-guided fine-needle aspiration (EUS-FNA) to determine the nature of left adrenal lesions. We described our experience in performing EUS-FNA of left adrenal lesions. CLINICAL PICTURE: During a 20-week period, data on consecutive patients who underwent EUS with or without EUS-FNA were prospectively captured. Patients with a left adrenal mass and who underwent EUS-FNA formed our study population. TREATMENT: EUS-FNA. OUTCOME: A total of 119 consecutive patients underwent diagnostic EUS +/- FNA, during which the left adrenal gland was routinely examined. Twelve of these patients underwent EUS as part of lung cancer staging and among these 12 lung cancer patients, 2 had left adrenal masses detected by computed tomography (CT). EUS detected left adrenal nodules in 2 other patients which were not visualised by CT. The overall prevalence of a left adrenal mass was 3.4%; in the subgroup with confirmed lung cancer, the prevalence was 33.3%. All 4 patients were male, with a mean age of 76.3 years (range, 67 to 87). The mean size of the left adrenal lesion was 30.4 mm (range, 9 to 84.8). EUS-FNA of the left adrenal lesions was performed under Doppler guidance. The mean number of needle passes was 2 (range, 1 to 4). A cellular aspirate was obtained in all patients. No procedural complications occurred. Metastatic non-small cell lung cancer was diagnosed in 2 patients, including a lesion missed on CT. For the other 2 cases, EUS-FNA revealed benign adrenal cells. CONCLUSIONS: EUS-FNA appears safe and useful for the evaluation of left adrenal masses.

Effect of spirometric maneuver, nasal clip, and submaximal inspiratory effort on measurement of exhaled nitric oxide levels in asthmatic patients.

STUDY OBJECTIVES: The measurement of exhaled nitric oxide (eNO) in asthmatic patients is increasingly being used to aid diagnosis and management. To standardize the measurement techniques, the American Thoracic Society and European Respiratory Society guidelines were published, but these were based mainly on expert opinions without strong clinical evidence on many aspects. We investigated the effect of three different factors on the on-line measurement of eNO. In a clinical setting, we evaluated the effect of prior spirometry, the use of nasal clips, and the influence of submaximal inspiratory effort on on-line eNO readings. Recommended guidelines on these factors have been published but have been supported by scanty research data. METHODS: Three groups of stable asthmatic patients (30 patients in each group) had eNO measurements made on-line (NIOX; Aerocrine AB; Solna, Sweden) before and 5 min after performing spirometric maneuvers, without and with a nasal clip, or with maximal and then submaximal inspiratory efforts. RESULTS: There were no significant differences in mean eNO levels among all three groups, before and after spirometry (68.2 vs 66.0 parts per billion [ppb], respectively; mean difference, 2.2 ppb; 95% confidence interval [CI], -0.4 to 4.9; p = 0.090), without use of a nasal clip compared with its use (46.7 vs 45.6 ppb, respectively; mean difference, 1.1 ppb; 95% CI, -0.7 to 2.8; p = 0.234), and maximal or submaximal inspiratory effort (52.6 vs 51.2 ppb, respectively; mean difference, 1.4 ppb; 95% CI, -0.3 to 3.0; p = 0.096). CONCLUSION: We conclude that on-line eNO measurements in clinical practice are not significantly affected by prior spirometry maneuver, use of a nasal clip, or submaximal inspiratory effort.

Atypical SARS in geriatric patient.

We describe an atypical presentation of severe acute respiratory syndrome (SARS) in a geriatric patient with multiple coexisting conditions. Interpretation of radiographic changes was confounded by cardiac failure, with resolution of fever causing delayed diagnosis and a cluster of cases. SARS should be considered even if a contact history is unavailable, during an ongoing outbreak.