SAD is an age-related disease that is more common in the elderly (13, 23), changes in the network of curled collagen fibers surrounding the alveolar duct and adjacent alveoli lead to dilatation of the alveolar duct and expansion of alveolar space, which in turn leads to alveolar enlargement.The result is a decrease in alveolar surface tension, leading to a decrease in alveolar compliance; and with age, a decrease in the vertebral body and a The convexity of the thorax also increases, Resulting in an increase in chest diameter. In addition, changes in the chest wall result in a decrease in the curvature of the diaphragm, which some extra thoracic causes lead to decreased respiratory muscle mass and reduced airway function(24).
Small airway disorders are gender-related, with THE wind in women, hazard ratio (OR = 1.545 95% CI 1.103–2.164) was higher than that of men, which was similar to other studies(25), A study in a mouse chronic obstructive pulmonary disease model showed, compared with male mice, Chronic smoke exposure increased the risk of airway remodeling in female mice, which could be prevented by removing the ovaries, it was suggested that oxidative stress, increased TGF-β1 signal transduction and the effect of estrogen were responsible for this phenomenon(26).
We analyzed the effect of family history of respiratory disease on SAD (OR = 1.481 95% CI 1.052–2.084), this result is consistent with the results of Okyere DO(27). Family history proved to be Interstitial lung disease, COPD, and asthma(28–30). In the Maas and ALSPAC Species, 77 single nucleotides were found to be associated with FEV1/FVC or FEV1 decline by genetic analysis(31).
Dust exposure history (OR = 1.723 95% CI 1.177–2.521) was also one of the risk factors for small airway obstruction. A 15-year follow-up of 9/11 survivors exposed to high concentrations of dust showed that they had higher airway responsiveness than the general population(32), Vasanthi R Sunil conducted research on this dust component in mice and found that dust exposure touch history leads to lung inflammation and oxidative stress and related to changes in lung Epigenetics and pulmonary dynamic(33). Multiple epidemiological studies have also verified the negative impact of dust exposure history on lung function(34–36).
Smoking is the most important preventable factor among many factors, and our study shows that smoking is associated with SAD (OR = 1.732 95% CI 1.231–2.436). Studies have shown that smoking and lung aging metabolism are the main causes of chronic obstructive pulmonary disease emphysema development, as demonstrated in a mouse model(37). Another pair of studies showed that in male subjects, smoking caused abnormal expression of several aging-related genes in small airway epithelial cells. Among smokers, the length of telomeres in small airway epithelial cells was significantly reduced by 14% compared with non-smokers(38). Chronic smoking can lead to inflammation, injury, tissue remodeling, and eventually airway dysfunction, which leads to airflow limitation and impaired alveolar ventilatio(39). Standardized smoking rates are reported to be high in China, with the proportion of current smokers at 26.0% (95% CI 25.8–26.2), and the standardized smoking rate for women under 40 years of age increased from 1.0% in 2003 to 1.6% in 2013. In addition, the prevalence of smoking among adolescents aged 15–24 increased from 8.3 per cent in 2003 to 12.5 per cent in 2013(40). However, in our smoking group, there was no significant difference between SAD and daily smoking amount (P = 0.104), smoking years (P = 0.192), and whether to quit smoking (P = 0.330), which is different from the results of other reports(13). I believe that no matter whether the daily smoking amount and smoking years are different, whether to quit smoking or not, the impairment of small airway function is irreversible. On the other hand, this conclusion may be related to the demographic differences of subjects(41), and its influence on small airway needs to be observed in further cohort studies.
There is little evidence on the relationship between SAD and pet ownership, from the Edith B Milanzi study we have, however, early childhood exposure to pets may slow the growth of FVC during adolescence(42), this correlation may be related to the Toxoplasma gondii(43). Other studies have found that owning a cat is associated with a reduced risk of childhood asthma, while owning rabbits and rodents is associated with an increased risk of childhood asthma(44), while the NHANES study showed that both cats and dogs may be allergens in the development of asthma(45). In our study, only small airway function was found to be associated with time spent with pets (OR = 1.499 95% CI 1.065–2.110), No significant differences were found between pet species (P = 0.32), and the mechanisms behind these differences deserve further study.
We also investigated the relationship between air pollutants and SAD. We recorded the air pollution level on that day and found that O3 level in the air was correlated with SAD (OR = 1.008 95%CI 1.003–1.013). This may be due to oxidative stress caused by acute exposure to ozone, increases in Nitric Oxide (NO) and other reactive nitrogen species in the lungs, which is then modified to produce S-nitroso mercaptan (SNO), changes the protein function and acts on macrophages, ultimately leading to the production of lung inflammation. However, no significant association was observed for SAD with other air pollutants, including PM2.5, PM10, SO2, CO, and NO2, which may be related to a lag effect(46), further research is needed to explore this correlation.
The evidence for an intrinsic link between SAD and asthma is sparse and inconclusive. In the Postma Dirkje S study, SAD was a risk factor for asthma and was present at all levels of asthma(47), particularly in patients with severe asthma, but another study identified asthma as a risk factor for small airway disorders(48), One study neutralizes the idea that inhaling allergic or non-allergic irritant causes inflammation or contraction of smooth muscles, which reduces their diameter and increases airway resistance, leading to SAD, SAD also accelerates the progression of Asthma(49). This view can also be applied to chronic bronchitis and emphysema. Chronic bronchitis is caused by goblet cell overproduction and secretion of excess mucus, which can lead to small airway lumen obstruction, epithelial remodeling, and airway surface changes in facial tension worsen airflow obstruction, which can lead to airway collapse, and SAD can exacerbate chronic bronchitis clinical manifestations(50), another study of emphysema in smokers showed that the occurrence of small airway obstruction was associated with the progression of emphysema. This may imply that airway dysfunction precedes lung function decline, and SAD may serve as an independent predictor of emphysema. Early identification and preventive treatment can limit the progression of emphysema(51).
We found no significant associations between SAD and tea consumption (P = 0.657), alcohol consumption (P = 0.855), exercise (P = 0.356), diabetes (P = 0.921), and hypertension (P = 0.952). The reasons may be as follows: 1. The research subjects are different. The subjects of this study are outpatients, and there is a certain bias. 2. This study is a cross-sectional study, which lacks causal correlation and includes many influencing factors. A larger sample size is needed to further explore the correlation. 3. The association between the above factors and lung function is overestimated, and further cohort studies are needed to observe the internal relationship between the above factors and SAD.
Our study has the following advantages: First, this is the first large-scale cross-sectional study of SAD in Xi'an. Second, this study included all age groups over the age of 18 and explored a wide range of living habits, health conditions and air pollution.
But our study has some limitations. First, our research objects are patients who visit the pulmonary function room of the hospital. Although pulmonary function testing has become a routine examination, the bias of the population cannot be ignored. Second, this study has most of the elephants are residents from Xi'an and surrounding towns, so the influence of environmental factors on the function of the small airway has not been explored. This effect proved to be non-negligible(52); secondly, we lack longitudinal data to substantiate some claims, including interventions such as smoking cessation, whether preventive measures really affect the progression of small airway disorders.