Longitudinal follow-up of the asthma status in a French–Canadian cohort & More Latest News Here – Up Jobs

The objective of this study was to analyze the evolution of asthma and related phenotypes in time by assessing new diagnoses as well as changes in the respiratory condition and comorbidities of a subsample of the SLSJ asthma family cohort. When considering changes in asthma status, seven new cases of asthma in this cohort’s subsample were found, representing 12% of individuals without asthma at recruitment. This is in line with the literature. Indeed, adult onset of asthma occurs in approximately 10% of the population^17,18. It is interesting to note that only one individual (#6) out of the seven has a profile in agreement with the Global Initiative for Asthma (GINA) guidelines for a non-asthmatic becoming asthmatic (atopy, methacholine PC₂₀ < 8 mg/ml and > 12% reversibility in airway obstruction following bronchodilators)⁴.

Atopy and BMI as risk factors of asthma

A study by Toskala et al. showed that atopy was a risk factor in the development and persistence of asthma¹⁹. This phenomenon was also observed in this study. Indeed, four of the seven individuals who developed asthma had allergies at recruitment and follow-up, and one developed atopy during this same period, representing 71% of the individuals with a new diagnosis of asthma. However, not all allergic asthma sufferers see their symptoms persist¹⁹. In fact, three individuals with asthma noticed their symptoms disappear and two of them were atopic at recruitment. The prevalence of allergic asthma phenotype considering all participants was persistent over time. The unchanged proportion of atopy phenotype in individuals with asthma at follow-up could be explained by the relatively stable concentration of IgE levels between the two periods (approximately 2.5 times higher than for individuals without asthma). This is consistent with the literature stating that deregulation of the immune system in allergic asthma results in elevated serum IgE levels¹⁹. It is remarkable that no significant change was observed for circulating IgE levels, regardless of age, asthma status, and medication, which evolved over the same period.

Another important risk factor is obesity²⁰. Obesity is often associated with an increase in the severity of asthma, onset of asthma in adults, and difficult asthma control due to a decreased response to medication^5,21. In the present study, an increase in BMI between recruitment and follow-up was observed in all groups. At follow-up, the average BMI was 27.06 kg/m², which is considered overweight. However, the average BMI of individuals with a change in their respiratory status was greater than 30 kg/m², which is considered obese. Four out of the seven individuals with adult-onset asthma had a BMI between 30 and 40 kg/m². Therefore, these individuals presented a significant risk factor linked to their new respiratory status.

Indices of asthma severity

The FEV₁/FVC ratio is a respiratory parameter that determines the degree of airway obstruction²², with a value usually lower than < 0.75–0.80 for asthmatic individuals, and that decreases according to the increase in asthma severity⁴. In this study, the mean FEV₁/FVC ratio decreased in both individuals with and without asthma over the years. Therefore, 54% of the decrease in FEV₁/FVC pre-BD ratio at follow-up can be explained by a regression model in the SLSJ subsample that includes values at recruitment for the percentage of BD reversibility, the percentage of predicted value of FEV1 and the percentage of eosinophils. A comparable effect of blood eosinophil on the decline of lung function was found in a population-based cohort of young adults in New Zealand among participants aged from 21 to 38 years old²³. The study determined that blood eosinophil counts were associated with a decrease of FEV₁/FVC ratio including participants with and without asthma²³. Additionally, in a population-based birth cohort that was followed into adulthood (until 26 years of age), a similar decrease in lung function in all groups, regardless of wheezing, sex, or other parameters were reported²⁴. It would therefore be normal to observe a decrease in lung capacity given the two decades between the two measurements.

The FEV₁/FVC values reflected the results of self-reported asthma severity in the questionnaire at follow-up. Individuals with asthma had an average FEV₁/FVC which corresponds to mild asthma according to the literature⁴, and the majority classified their asthma as very mild or mild. The severity of asthma can also be determined by the class of medication taken to relieve symptoms and exacerbations⁴. The medication prescribed in the subsample is primarily short-acting beta-agonists and ICSs, which also correspond to mild asthma⁴. However, there has been a marked increase (31%) in the prescription of long-acting beta-agonists, usually prescribed to people with moderate asthma⁴, and the prescription of ICSs (11%) at follow-up. The changes in respiratory medication use could be due to the modifications in the GINA guidelines since recruitment; in 2019 ICS-formoterol was recommended in intermittent asthma and mild persistent asthma⁴. Whereas in the 2002 GINA report ICSs were recommended to be introduced in mild persistent asthma only⁴. This could indicate that the symptoms are well controlled by the medication, leading to a self-reported asthma severity by the participants as very mild and mild.

Smoking has a significant impact on asthma, for example through epigenetic changes³. The number of smokers significantly decreased (from 22 to 4) between recruitment and follow-up. However, the risk of developing asthma in adulthood due to this exposure remains³. For individuals who had a new status of asthma at follow-up, five out of seven participants were either ex-smokers or smokers. Moreover, 58% of the 24 individuals with adult-onset asthma at recruitment were either ex-smokers or smokers. Among the 24 individuals at recruitment and the 7 individuals at follow-up with adult-onset asthma, 4 have developed obstructive sleep apnea and 3 have or had psychological disturbances (depression and anxiety disorder). These comorbidities can be found in people with severe asthma as can gastro-esophageal reflux disease and chronic infections and may be associated with difficult asthma outcomes^25,26. Respiratory infections noted for these participants were not recurrent or chronic. Since the SLSJ asthma family cohort is mainly comprised of participants with mild-to-moderate asthma it is expected to have little comorbidities in the subsample.

Development of COPD among asthmatic participants

A study by Mirabelli et al. demonstrated the presence of COPD in 29% of a population with a history of asthma²⁷. Individuals with asthma who smoked are more likely to develop COPD as they age and thus may develop asthma-COPD overlap (ACO) phenotypes^3,28. In this study, five participants who were asthmatic at recruitment (7%) developed COPD and all of them were ex-smokers or smokers. For all of them, PC₂₀ was also very low at recruitment, four of the five individuals who developed COPD had values less than 0.25 mg/ml which corresponds to severe AHR, and one had a value of 0.5 mg/ml, which is considered moderate AHR²⁹. This suggests that this risk factor may have contributed to the development of COPD^30,31. These results contribute to a better understanding of ACO which is critical since patients affected by both diseases have more exacerbations, poorer quality of life, and faster decline in lung function, as well as a higher death rate than patients with only asthma or COPD^{22,32,33,34,35}.

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