Clinical Subtypes of Neutrophilic Asthma: A Cluster Analysis From Australasian Severe Asthma Network.

BACKGROUND: Clinical heterogeneity may exist within asthma subtypes defined by inflammatory markers. However, the heterogeneity of neutrophilic asthma (NA) remains largely unexplored. OBJECTIVE: To explore potential clusters and the stability of NA. METHODS: Participants with NA from the Australasian Severe Asthma Network underwent a multidimensional assessment. They were then asked to participate in a 12-month longitudinal cohort study. We explored potential clusters using a hierarchical cluster analysis and validated the differential future risk of asthma exacerbations in the identified clusters. A decision tree analysis was developed to predict cluster assignments. Finally, the stability of prespecified clusters was examined within 1 month. RESULTS: Three clusters were identified in 149 patients with NA. Cluster 1 (n = 99; 66.4%) was characterized by female-predominant nonsmokers with well-controlled NA, cluster 2 (n = 16; 10.7%) by individuals with comorbid anxiety/depressive symptoms with poorly controlled NA, and cluster 3 by older male smokers with late-onset NA. Cluster 2 had a greater proportion of participants with severe exacerbations (P = .005), hospitalization (P = .010), and unscheduled visits (P = .013) and a higher number of emergency room visits (P = .039) than that of the other two clusters. The decision tree assigned 92.6% of participants correctly. Most participants (87.5%; n = 7) in cluster 2 had a stable NA phenotype, whereas participants of clusters 1 and 3 had variable phenotypes. CONCLUSIONS: We identified three clinical clusters of NA, in which cluster 2 represents an uncontrolled and stable NA subtype with an elevated risk of exacerbations. These findings have clinical implications for the management of NA.

Interaction effect of chronic cough and ageing on increased risk of exacerbation in patients with asthma: a prospective cohort study in a real-world setting.

Background: Older adults with asthma have the greatest burden and worst outcomes, and there is increasing evidence that chronic cough (CC) is associated with asthma severity and poor prognosis. However, the clinical characteristics of older adult patients with both asthma and CC remain largely unknown. Methods: Participants with stable asthma underwent two cough assessments within 3 months to define the presence of CC. Patients were divided into four groups based on CC and age (cut-off ≥60 years). Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to investigate asthma exacerbations. Logistic regression models were used to explore the interaction effect of CC and age on asthma control and exacerbations. Results: In total, 310 adult patients were prospectively recruited and divided into four groups: older CC group (n=46), older non-CC group (n=20), younger CC group (n=112) and younger non-CC group (n=132). Compared with the younger non-CC group, the older CC group had worse asthma control and quality of life and increased airflow obstruction. The older CC group showed an increase in moderate-to-severe exacerbations during the 12-month follow-up. There was a significant interaction effect of CC and ageing on the increased moderate-to-severe exacerbations (adjusted risk ratio 2.36, 95% CI 1.47-3.30). Conclusion: Older asthma patients with CC have worse clinical outcomes, including worse asthma control and quality of life, increased airway obstruction and more frequent moderate-to-severe exacerbations, which can be partly explained by the interaction between CC and ageing.

Association between ventilatory ratio and ICU mortality in interstitial lung disease patients on mechanical ventilation: A retrospective study.

BACKGROUND: Ventilatory ratio (VR) is a simple bedside index of ventilatory efficiency. Interstitial lung disease (ILD) is a diverse group of diseases that causes fibrosis or inflammation of the pulmonary parenchyma, and the main clinical manifestation is hypoxemia. To date, no study has explored ventilation efficiency in patients with ILD. OBJECTIVES: This study aimed to explore the features of VR in mechanically ventilated patients with ILD and their relationship with intensive care unit (ICU) mortality. METHODS: In this retrospective analysis, we included mechanically ventilated patients with ILD in the ICU of West China Hospital, Sichuan University, from 2013 to 2021. Demographic data and mechanical ventilation (MV) parameters within 24 h of intubation were collected. The characteristics of VR and their relationships with ICU mortality were also analyzed. RESULTS: 224 patients were included in the final analysis. There were 146 males (53.9%), and the median age was 65 years (interquartile range [IQR]54∼74). The mean value of VR was 2.22, and VR was significantly higher in nonsurvivors than in survivors (1.79 vs 2.32, P < 0.001). A high VR value was an independent risk factor for ICU mortality (odds ratio=1.602, P = 0.038) after adjustment. A high value of VR was associated with a shorter survival time after admission to ICU (hazard ratio=1.485, P = 0.006) CONCLUSIONS: VR in patients with ILD on MV was increased, and the VR of nonsurvivors within 24 h of intubation was higher than that of survivors. The high VR value within 24 h of intubation was an independent risk factor for ICU mortality after adjusting for other factors.

Self-Reported Insufficient Sleep Is Associated With Clinical and Inflammatory Features of Asthma: A Prospective Cohort Study.

BACKGROUND: A few studies have explored the association between short sleep duration and worse asthma outcomes in patients with self-reported asthma; however, all of them were cross-sectional. OBJECTIVES: To investigate the association between self-reported sleep duration and asthma-related clinical and inflammatory characteristics and whether sleep duration is associated with asthma exacerbations (AEs) in the following year. METHODS: A prospective cohort study consecutively recruited participants with asthma, who were classified into short (n = 58), normal (n = 380), and long (n = 84) sleep duration groups. We investigated the clinical and inflammatory characteristics and exacerbations within a 1-year follow-up. RESULTS: Patients with short sleep duration were older and had significantly lower total IgE and FeNO levels and higher airway inflammation, characterized by increased levels of IL-6 and TNF-α in sputum than those of patients with normal sleep duration. Furthermore, they had a significantly increased risk for poorly controlled asthma (adjusted odds ratio = 2.741; 95% CI, 1.379-5.447; P = .004) and moderate to severe AEs (adjusted incidence rate ratio = 1.798; 95% CI, 1.098-2.942; P = .020). CONCLUSIONS: Short sleep duration was associated with non-type 2 inflammation and is an independent risk factor for future AEs. Therefore, as a potentially treatable trait, sleep duration may have clinical implications for asthma management.

Endogenous Adenosine 5'-Monophosphate, But Not Acetylcholine or Histamine, is Associated with Asthma Control, Quality of Life, and Exacerbations.

OBJECTIVE: Endogenous adenosine 5'-monophosphate (AMP), acetylcholine (ACh), and histamine (HA) are known to be important in bronchial contraction, but their clinical relevance to asthma is poorly understood. We aimed to quantify endogenous AMP, ACh, and HA in induced sputum samples and explore their relationships with asthma control and exacerbations. METHODS: 20 healthy subjects and 112 asthmatics underwent clinical assessment, sputum induction, and blood sampling. The level of asthma control was determined by the asthma control test (ACT) questionnaire. Asthma exacerbation was evaluated according to the criteria of the American Thoracic Society/European Respiratory Society. Levels of AMP, ACh, and HA in sputum were measured by liquid chromatography coupled to tandem mass spectrometry. IL-ß, IL-4, IL-5, IL-6, IL-8, IL-13, IL-17A, TNF-α, IFN-γ, and macrophage-derived chemokine (MDC) were also measured. RESULTS: Compared to healthy controls, asthmatics had higher levels of HA, lower levels of ACh, and similar levels of AMP in induced sputum samples. Compared to controlled asthma (n = 54), uncontrolled asthma (n = 58) showed higher AMP levels (P = 0.002), but similar HA and ACh levels. AMP was negatively correlated with ACT scores (r = - 0.348) and asthma quality of life questionnaire scores (r = - 0.188) and positively correlated with blood monocytes percentage (r = 0.195), sputum MDC (r = 0.214), and IL-6 levels (r = 0.196). Furthermore, AMP was associated with an increased risk of exacerbations in the preceding year. CONCLUSION: Endogenous AMP, but not ACh or HA, was associated with asthma control, quality of life, and exacerbations in the previous year, which indicates that AMP could be a clinically useful biomarker of asthma.

Sputum Metabolomic Profiling Reveals Metabolic Pathways and Signatures Associated With Inflammatory Phenotypes in Patients With Asthma.

PURPOSE: The molecular links between metabolism and inflammation that drive different inflammatory phenotypes in asthma are poorly understood. We aimed to identify the metabolic signatures and underlying molecular pathways of different inflammatory asthma phenotypes. METHODS: In the discovery set (n = 119), untargeted ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was applied to characterize the induced sputum metabolic profiles of asthmatic patients with different inflammatory phenotypes using orthogonal partial least-squares discriminant analysis (OPLS-DA), and pathway topology enrichment analysis. In the validation set (n = 114), differential metabolites were selected to perform targeted quantification. Correlations between targeted metabolites and clinical indices in asthmatic patients were analyzed. Logistic and negative binomial regression models were established to assess the association between metabolites and severe asthma exacerbations. RESULTS: Seventy-seven differential metabolites were identified in the discovery set. Pathway topology analysis uncovered that histidine metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, linoleic acid metabolism as well as phenylalanine, tyrosine and tryptophan biosynthesis were involved in the pathogenesis of different asthma phenotypes. In the validation set, 24 targeted quantification metabolites were significantly expressed between asthma inflammatory phenotypes. Finally, adenosine 5'-monophosphate (adjusted relative risk [adj RR] = 1.000; 95% confidence interval [CI] = 1.000-1.000; P = 0.050), allantoin (adj RR = 1.000; 95% CI = 1.000-1.000; P = 0.043) and nicotinamide (adj RR = 1.001; 95% CI = 1.000-1.002; P = 0.021) were demonstrated to predict severe asthma exacerbation rates. CONCLUSIONS: Different inflammatory asthma phenotypes have specific metabolic profiles in induced sputum. The potential metabolic signatures may identify therapeutic targets in different inflammatory asthma phenotypes.

Chronic cough in asthma is associated with increased airway inflammation, more comorbidities, and worse clinical outcomes.

Background: Cough is often the most prominent and intractable symptom reported by patients with asthma, but few studies have explored the characteristics of patients with asthma and with chronic cough (CC) in a real-world setting. Methods: In a prospective cohort study, patients ages ≥ 18 years with stable asthma were consecutively recruited at the West China Hospital, Sichuan University. The patients were classified as having asthma with CC (the CC group) or asthma with non-CC (the non-CC group) after 3 months of optimized asthma therapy according to standard guidelines. Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to assess asthma exacerbations. Results: Of 323 patients with asthma, 127 patients were assigned to the CC group and 196 patients were assigned to the non-CC group. The participants with CC were older and had more airflow obstruction; worse asthma control and quality of life; increased airway inflammation; upper respiratory tract infection as a trigger; and more comorbidities, such as psychological dysfunction, rhinitis, chronic obstructive pulmonary disease, and bronchiectasis. They reported greater work productivity loss and daily activity impairment, and increased moderate-to-severe exacerbations. Conclusion: The participants with asthma and with CC had a significant disease burden, with increased exacerbations, health-care utilization, and impaired work productivity and daily activity. These observations indicated potential clinical implications in patients with asthma and with CC, and call for more attention to this aspect of asthma.

Clinical characteristics and postoperative outcomes of systemic artery-to-pulmonary vessel fistula in hemoptysis patients.

OBJECTIVES: To investigate the clinical characteristics and outcomes on the success of bronchial arterial embolization (BAE) in patients with and without systemic artery-to-pulmonary vessel fistula (SA-PF) and to evaluate the feasibility of CTA in the assessment of SA-PF. METHODS: We retrospectively enrolled 420 consecutive patients that underwent BAE for hemoptysis control in our hospital from September 2011 to May 2019. The clinical characteristics, preprocedural CTA findings, BAE procedural findings, and follow-up outcomes were collected. Patients were divided into two groups according to DSA findings: patients with SA-PF and those without. RESULTS: A total of 184 (43.7%) patients presented with SA-PF. Pneumonia was less likely to be the concomitant condition in patients with SA-PF (p < 0.001). The mean number of culprit arteries per patient was significantly higher in patients with SA-PF compared to that in patients without SA-PF (p = 0.017). The SA-PF patients saw a greater probability of recurrence (HR: 2.782, 95% CI: 1.617-4.784, p < 0.001). SA-pulmonary venous fistula (SA-PVF) favored lower hemoptysis recurrence rate (HR: 0.199, 95%CI: 0.052-0.765, p = 0.019). SA-pulmonary artery fistula (SA-PAF) can be detected by optimized CTA protocol with a detection rate of 65.3% (49/75). CONCLUSIONS: The presence of SA-PF is an independent risk factor predicting early recurrence of hemoptysis after BAE. SA-PVF seems to be a protective factor for longer hemoptysis control compared to SA-PAF. Optimized preprocedural CTA is a reliable examination to identify SA-PAF. KEY POINTS: • The appearance of SA-PF is associated with a greater probability of early recurrent hemoptysis after bronchial artery embolization. • The presence of SA-PVF seems to be a protective factor for longer hemoptysis control after BAE compared to SA-PAF. • Optimized CTA protocol seems to be a promising auxiliary examination to detect SA-PAF.

CT-guided transthoracic pulmonary artery catheterization: an experimental study in a porcine model.

OBJECTIVES: We investigated the safety and feasibility of CT-guided transthoracic pulmonary artery catheterization (TPAC) in a porcine model. METHODS: Procedures were conducted on ten mature Bama miniature pigs. After anesthesia, chest CT was performed in the left lateral decubitus position to determine the puncture route. Under the guidance of multiple CT scans, the introducer sheath was inserted from the right chest wall of the pig into the right pulmonary artery using the Seldinger technique. Then, a catheter connected with a transducer was inserted into the sheath to measure the pulmonary artery pressure. Finally, an active approximator was used to close the puncture site on the pulmonary artery. The pigs were followed up for 8 weeks to evaluate the operation-related complications and survival. RESULTS: Ten of 11 CT-guided TPAC procedures were successfully performed on ten pigs, rendering a technical success rate of 90.9%. One pig had hemoptysis while the needle was being inserted during the first operation, and a second procedure was successfully conducted 17 days later. Other complications, including pulmonary bleeding along the needle track (3 of 11; 27.3%), unclosed pulmonary artery puncture sites (3 of 10; 30%), pneumothorax (1 of 11; 9.1%), and hemopericardium (1 of 11; 9.1%), spontaneously resolved without complication-specific treatment. The mean pulmonary arterial pressure was 32 ± 17.6 mmHg. All animals survived the procedure and reached the end of the follow-up period. CONCLUSIONS: CT-guided TPAC is feasible and safe in a porcine model, serving as a potential alternative pathway for pulmonary artery intervention. KEY POINTS: • TPAC is feasible and safe in a porcine model, serving as a potential alternative pathway for pulmonary artery intervention. • This novel approach allows for faster access to the pulmonary artery, and it might be easier to operate the tip of the catheter to super-select the intent branch of the pulmonary artery. • TPAC can be an alternative pulmonary artery intervention pathway in patients with mechanical right-heart valves, great-vessel transposition, and other obstacles.

Increased microRNA-30a levels in bronchoalveolar lavage fluid as a diagnostic biomarker for lung cancer.

BACKGROUND: MicroRNA-30a (miRNA-30a) levels have been shown to increase in the plasma of lung cancer patients. Herein, we evaluated the miRNA-30a levels in the bronchoalveolar lavage fluid (BALF) of lung cancer patients as a potential biomarker for lung cancer diagnosis. METHODS: BALF miRNA-30a expression of 174 subjects was quantified using quantitative real-time reverse transcription-polymerase chain reaction and compared between lung cancer patients and control patients with benign lung diseases. Moreover, its diagnostic value was evaluated by performing receiver operating characteristic (ROC) curve analysis. RESULTS: The relative BALF miRNA-30a expression was significantly higher in the lung cancer patients than in the controls (0.74 ±  0.55 versus 0.07 ±  0.48, respectively, p < 0.001) as well as in lung cancer patients with stage I-IIA disease than in those with stage IIB-IV disease (0.98 ±  0.64 versus 0.66 ±  0.54, respectively, p < 0.05). Additionally, miRNA-30a distinguished benign lung diseases from lung cancers, with an area under the ROC curve (AUC) of 0.822. ROC analysis also revealed an AUC of 0.875 for the Youden index-based optimal cut-off points for stage I-IIA adenocarcinoma. Thus, increased miRNA-30a levels in BALF may be a useful biomarker for non-small-cell lung cancer diagnosis.

Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis.

BACKGROUND: There is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic. METHODS: The Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes. RESULTS: The Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64). CONCLUSIONS: The worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.

Impulse oscillometry for detection of small airway dysfunction in subjects with chronic respiratory symptoms and preserved pulmonary function.

BACKGROUND: Subjects with chronic respiratory symptoms and preserved pulmonary function (PPF) may have small airway dysfunction (SAD). As the most common means to detect SAD, spirometry needs good cooperation and its reliability is controversial. Impulse oscillometry (IOS) may complete the deficiency of spirometry and have higher sensitivity. We aimed to explore the diagnostic value of IOS to detect SAD in symptomatic subjects with PPF. METHODS: The evaluation of symptoms, spirometry and IOS results in 209 subjects with chronic respiratory symptoms and PPF were assessed. ROC curves of IOS to detect SAD were analyzed. RESULTS: 209 subjects with chronic respiratory symptoms and PPF were included. Subjects who reported sputum had higher R5-R20 and Fres than those who didn't. Subjects with dyspnea had higher R5, R5-R20 and AX than those without. CAT and mMRC scores correlated better with IOS parameters than with spirometry. R5, R5-R20, AX and Fres in subjects with SAD (n = 42) significantly increased compared to those without. Cutoff values for IOS parameters to detect SAD were 0.30 kPa/L s for R5, 0.015 kPa/L s for R5-R20, 0.30 kPa/L for AX and 11.23 Hz for Fres. Fres has the largest AUC (0.665, P = 0.001) among these parameters. Compared with spirometry, prevalence of SAD was higher when measured with IOS. R5 could detect the most SAD subjects with a prevalence of 60.77% and a sensitivity of 81% (AUC = 0.659, P = 0.002). CONCLUSION: IOS is more sensitive to detect SAD than spirometry in subjects with chronic respiratory symptoms and PPF, and it correlates better with symptoms. IOS could be an additional method for SAD detection in the early stage of diseases.

Prevention and treatment system of novel coronavirus infection in medical and health institutions: experience in West China Hospital of Sichuan University.

The novel coronavirus infection broke out in Wuhan, China, in December 2019, and progressed to a global pandemic. We describe the measures taken by West China Hospital of Sichuan University to address the diagnosis, prevention and treatment of the infection.

Extraction of pulmonary Trachea by dynamic tubular edge contour algorithm.

BACKGROUND: One of the difficulties and hot topics in the field of computer vision and image processing is extraction of the high-level pulmonary trachea from patients' lung CT images. Current, common bronchial extraction methods are limited by the phenomenon of bronchial loss and leakage, and cannot extract the higher-level pulmonary trachea, which does not meet the requirements of guiding lung puncture procedures. METHODS: Based on the characteristic "tubular structure" (ring or semi-closed ring) of the pulmonary trachea in CT images, an algorithm based on dynamic tubular edge contour is proposed. In axial, coronal and sagittal CT images, the algorithm could extract the skeletal line of the pulmonary trachea and vessel-connecting region, perform elliptical fitting, extract the pulmonary trachea by the ratio of the ellipse's long and short axes, and obtain point cloud data of the pulmonary trachea in three directions. The point cloud data was fused to obtain a complete three-dimensional model of the pulmonary trachea. RESULTS: The algorithm was verified using CT data from "EXACT09", and could extract the pulmonary trachea to the 10-11 level, which effectively solves the problems of leakage and loss of the trachea. CONCLUSIONS: We have constructed a novel extraction algorithm of pulmonary trachea that can guide the doctors to decide the puncture path and avoid the large trachea, which has important theoretical and practical significance for reducing puncture complications and the mortality rate.

Plasma miR-30a-5p as an early novel noninvasive diagnostic and prognostic biomarker for lung cancer.

Aim: Circulation miRNAs have become increasingly appreciated in the diagnosis and prognosis of lung cancer. This study aims to identify and evaluate plasma miRNA-30a-5p as an early noninvasive biomarker for the diagnosis and prognosis of lung cancer. Pateints & methods: Expression levels of plasma miRNA 30a-5p were measured by quantitative real-time PCR. Receiver operating characteristic analysis and area under the curve were used to differentiate malignant from benign tumors and from healthy controls. Kaplan-Meier curves and Cox regression were used to determine survival and prognosis. Results: Our results suggest that the level of miRNA-30a-5p in plasma might be a considerable early novel noninvasive diagnostic and prognostic biomarker for lung cancer. Conclusion: Prospective studies must be performed to confirm this new early novel noninvasive diagnostic and prognostic biomarker for lung cancer.

Dupilumab treatment in moderate-to-severe atopic dermatitis: A systematic review and meta-analysis.

BACKGROUND: Dupilumab, a fully human monoclonal antibody against the interleukin-4-receptor α subunit, has been developed and used in clinical trials to treat atopic dermatitis (AD). OBJECTIVE: We aimed to assess the overall efficacy and safety of dupilumab treatment in AD. METHODS: PubMed, Embase, Cochrane library databases, and the Chinese Biological Medicine (CBM) published up to September 2017 were searched. All randomized controlled trials (RCTs) of dupilumab treatment on adult patients with AD were included. Fixed- or random-effects models were used to calculate pooled standard mean differences or relative risks (SMD or RR, respectively). RESULTS: Six trials involving 2447 patients were identified. Pooled analysis revealed significant improvements in Eczema Area and Severity Index (EASI) score (SMD = -0.89, 95% CI: -1.0 to -0.78), percentage of body surface area (BSA) (SMD = -0.83, 95% CI: -0.90 to -0.75), pruritus numeric rating scale (NRS) scores (SMD = -0.81, 95% CI: -0.96 to -0.66), and Dermatology Life Quality Index (DLQI) scores (SMD = -0.78, 95% CI: -0.89 to -0.66). Dupilumab treatment was also associated with a significant increase in the proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.82; 95% CI: 3.23 to 4.51) and a similar incidence of adverse events (RR = 1.0; 95% CI: 0.96 to 1.04). CONCLUSIONS: Our analysis provided evidence that dupilumab had an acceptable safety profile and resulted in clinically relevant improvements in signs and symptoms of AD. Dose regimens of 300 mg qw and q2 w seemed to have similar benefits. Further long-term trials are required for confirmation.

Identification and validation of asthma phenotypes in Chinese population using cluster analysis.

BACKGROUND: Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. OBJECTIVE: To identify and prospectively validate asthma clusters in a Chinese population. METHODS: Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. RESULTS: Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07-3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26-40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02-4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95-69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission (P < .0001 for all comparisons). CONCLUSION: We identified 3 clinical clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries.