Identification of Asthma Phenotypes in the Spanish MEGA Cohort Study Using Cluster Analysis

Introduction: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes. Methods: We performed a multicentre prospective cohort study, including adult patients with asthma (N=512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm. Results: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities. Conclusion: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps. (AU)

Fisiología y fisiopatología de la vía aérea pequeña en el asma / Physiology and physiopathology of the distal airways in asthma

Las vías aéreas pequeñas (VAP) son aquellas que tienen un diámetro interno menor de 2 mm. Aunque en sujetossanos su contribución a la resistencia total al flujo aéreo es discreta, en asmáticos podrían ser responsablesdel 50-90 % de la resistencia total al flujo aéreo.La reducción de los flujos mesoespiratorios e instantáneos ha constituido el principal instrumento para sospecharenfermedad de la VAP, aunque su notable variabilidad y la ausencia de un punto de corte suficientementevalidado le resta aplicación clínica.Los volúmenes pulmonares estáticos pueden aportar información indirecta sobre el estado de las vías aéreasmás distales evidenciando dos consecuencias de su alteración: el atrapamiento aéreo y la hiperinsuflacióndinámica.Mientras que la determinación de las resistencias de las vías aéreas por pletismografía y de las resistencias delsistema respiratorio por interrupción al flujo resultan muy inespecíficas, la técnica de la oscilación forzadapermite discriminar obstrucción de las VAP frente a las de mediano calibre. El patrón característico de obstrucciónperiférica comprende el descenso de la resistencia dependiente de la frecuencia, la disminución dela reactancia y el incremento de la frecuencia de resonancia.El lavado de nitrógeno mediante respiración única o por reinhalación múltiple también proporciona informaciónespecífica de las VAP, aunque la disponibilidad de este tipo de equipos es menor.El análisis mediante modelos bicompartimentales del óxido nítrico exhalado permite la determinación dela concentración alveolar de óxido nítrico, que parece aportar información sobre la actividad inflamatoria enla VAP(AU)

The small airways are those with an internal diameter of less than 2 mm. The contribution of these airways tototal airflow resistance is small in healthy individuals but can represent 50-90 % of total airflow resistance inasthmatics. Suspicion of small airways disease has been based on reduction of midexpiratory andinstantaneous flows, although wide variability in their values and the absence of a sufficiently validatedcut-off point has limited their clinical application. Static pulmonary volumes can provide indirect evidence ofthe state of the most distal airways, revealing two effects of their alteration: air trapping and dynamichyperinflation. While determination of airway resistance by plethysmography and of respiratory systemresistance measured by flow interruption are highly non-specific, the forced oscillation technique allowsobstruction of the small airways to be distinguished from that of medium-caliber airways. The characteristicpattern of peripheral obstruction includes a decrease in frequency-dependent resistance, reduced reactivityand an increase in resonance frequency. Single-or multiple-breath nitrogen washout can also provide specificinformation on the small airways, although the apparatus required is less frequently available. Analysisthrough bicompartmental models of exhaled nitric oxide allows alveolar nitric oxide concentrations to bedetermined, which seems to provide information on inflammatory activity in the small airways(AU)