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Introduction to Airway Variants
Computed tomography (CT) is transforming the way clinicians view the etiology of chronic obstructive pulmonary disease (COPD). Clinicians are examining how variations in airway branches might influence the course of COPD, which kills more than 3 million people worldwide each year, or 5% of the global population.1,2
“We want to determine if COPD that is related to these airway variants has a different prognosis from COPD due to smoking,” explained Benjamin M. Smith, MD, MSc, assistant professor of respiratory medicine from McGill University in Montreal, Quebec, Canada, in an email interview with Pulmonology Advisor. “If we find a different prognosis, we could use these easily detected airway variants to help us identify people with worse prognosis who are more likely to benefit from therapy (ie, precision medicine). Similarly, if these airway branch variants can predict who will develop COPD, we might also be able to use this information to guide disease prevention strategies.”
In an analysis of 2 major COPD trials (N=5054 participants), the Multi-Ethnic Study of Atherosclerosis (MESA; ClinicalTrials.gov Identifier: NCT00005487) and Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS; ClinicalTrials.gov Identifier: NCT01969344), Dr Smith and colleagues sought to classify the type of airway branch variation that results in a COPD diagnosis. The team found that airway branch variations occurred in 26.5% of MESA participants (n=3169), and that the most common variation was an accessory subsuperior airway (16.0%; 95% CI, 14.6%-17.2%), followed by absent right medial-basal airway (6.1%; 95% CI, 5.3%-6.9%).1
In the pooled analysis, the odds ratio (OR) of an accessory subsuperior segmental airway associated with was 1.40 (95% CI, 1.19-1.64; P <.001). This association did not change significantly when adjusted for age, sex, weight, smoking, and ethnicity or race.1
The second-most common airway variant (absence of the right medial-basal segmental airway) did not correlate with COPD in the MESA study. In smokers, however, the OR for COPD was 2.04 (95% CI, 1.13-3.71; P =.019). In the SPIROMICS study, the airway variant and smoking association had an OR of 1.71 (95% CI, 1.19-2.47; P =.004). Between the 2 studies, the OR for COPD was 1.55 (95% CI, 1.15-2.08; P =.004), and for smokers, it was 1.78 (95% CI, 1.27-2.49; P <.001).1
The 2 variants also produced different clinical presentations. The accessory subsuperior airway was associated with chronic bronchitis with a productive cough, whereas the absence of a right medial-basal airway was associated with dyspnea. Patients with the accessory subsuperior airway variant had worse scores on the COPD Assessment Test, as well as the St. George Respiratory Questionnaire, compared with patients who had the absence of a right medial-basal airway.1
The airway variants were associated with other anatomical features. Patients with accessory subsuperior airways tended to have shorter airway segments throughout the lungs compared with patients with standard anatomy. In patients with an absence of right medial-basal airway, the airway lumens were smaller throughout the lungs compared with those who had standard anatomy. Small airway lumens could determine the airflow and explain the higher prevalence of dyspnea in this cohort.1
Ethnicity determined the type of airway variant. An accessory subsuperior segmental airway was more common in white patients, whereas absent right medial-basal airway was more common in Asian Americans and less common in African Americans.1
During a 10-year span, the researchers discovered that the airway variants had not changed. They also found a familial association in airway variation, suggesting a genetic component, the most common polymorphism being the FGF10 gene.1
Looking Beyond Smoking for COPD Clues
Once thought of as a preventable disease caused by smoking, COPD is now regarded as a heterogeneous disease with multiple origins.1 Not every smoker develops COPD, and the disease has also been found in never-smokers.1 Depending on the variation in airway branch, clinicians might be able to predict outcomes as well as the patients most likely to benefit from treatment and prevention.
