In this study we aimed to characterize the clinical, lung function, inflammatory and immunological characteristics of older persons with the main OLD, namely asthma and COPD. These diseases were defined as reported by other authors and participants were allocated in different groups in order to assess differences between them. Additionally, we determined different cytokines related with Th-1 and Th-2 pathways.
Asthma prevalence, defined as the combined frequency of asthma diagnosis reported in lifetime and wheezing within the last 12 months plus reversibility was 8%, which is according to the Portuguese National Asthma Survey[24] data for this age group.
In our sample, the frequency of COPD according to GOLD definition was 32.5%. Our results are similar with data from the Portuguese BOLD study that estimated COPD prevalence in people older than 70 years of 30.8% [10], using also the fixed FEV1/FVC ratio criteria. The fixed ratio criteria may overdiagnoses COPD in elderly, although we already showed in a previous study that in this age group, spirometry interpretation is highly influenced by the reference equations used and meaningful differences may be found[15] when using the lower limit of normality. This is in agreement with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report 2020[8].
COPD represented the most frequent OLD, which is not surprising considering the physiologic lung function decline associated with age [25] that compromises mostly the FEV1. This might have contributed also for the high frequency of patients with both asthma and COPD traits, previously classified as ACO (5.2%) as compared to other authors that have used the same definition as we, namely in PLATINO [22] and PUMA [23] studies.
There were different ACO definitions available in the literature and consensual one was been not established[26][27]. This has contributed to the wide prevalence range found in population based studies and in asthma and COPD patient surveys[28]. Most definitions were based in phenotypic features and a biomarker is still lacking. In our study, higher levels of TNF-α were associated with the presence of asthma and COPD traits in the same patient. Higher levels of TNF-α have been related with the severity of airway obstruction in COPD patients [29] which may explain our findings as patients with both diseases presented more severe airways obstruction.
To the moment, no single endotype of asthma or COPD has been fully characterized in elderly. Despite the lack of strong evidence, the presence of Th-2 inflammation allows to classify asthma as Th-2 “high” or Th-2”low” endotypes, as proposed by Wenzel S. Th-2 “high” is associated with a better response to inhaled corticosteroids[30].
More recently, it was considered that type 2 inflammation may constitute also a distinct endotype in COPD, similar to the asthma Th-2 “high” endotype. Other existent COPD endotypes seem to be related with Th-1 inflammation and type 17 helper T cells [31].
Previous studies also found diverse inflammatory patterns in asthma, COPD and may overlap in certain patients, leading to a mixture of Th-2 and non-Th-2 cytokine expression. Patients with asthma and COPD may show therefore diverse inflammatory processes that overlap the characteristics of both conditions. For this reason the previously ACO entity cannot be considered a specific phenotype of asthma or COPD but a blend of both components[32], [33].
Our findings suggest that at least in this age group COPD and asthma are heterogenous in terms of immunological endotype and Th-1 and Th-2 cytokines are common independently of the considered disease, even in COPD.
Patients with both asthma and COPD traits / clinical features patients have been considered to present an increased risk of exacerbation and hospitalization [22] as they usually present more severe disease. We found lower lung function parameters and more frequent non-scheduled visits to a doctor in this group, indicating that this phenotypic presentation should raise awareness. According to our results this is particularly relevant as patients with features of both diseases presented a future risk of exacerbations. This trend for increased risk of healthcare utilizations has been previously reported[34].
Surprisingly, COPD patients reported the best SGRQ results. This might be related with the characteristics of our sample, as older patients tend to have substantial comorbidities and to be less active, which may have contributed for a wrong perception of the real burden of COPD on the quality of life.
According to the literature, comorbidities are increased in patients with asthma and COPD features compared to other obstructive airway diseases [26], mainly in smokers. In our study we could not find this association probably due to the high “baseline” degree of comorbidities among this age group.
The major strengths of our study are the inclusion of a carefully selected sample of older persons with the main OLD recruited in a non-clinical setting, the detailed characterization in terms quality of life, disease control, comorbidities, lung function, airways inflammation and cytokine assessment. Additionally, we were able to assess the future risk in these patients. To our knowledge, this is the first study providing such information in older persons.
We were not able to include a high number of patients with asthma or asthma and COPD traits and this constitute a limitation. Additionally, we do not know to which extent these results could be extrapolated. However, we found that the presence of asthma and COPD traits in the same patient is associated with worst lung function, more non-scheduled visits to a doctor and with a higher level of TNF-α.