The 2017 Global Burden of Disease Study reported that chronic pulmonary diseases are among the primary causes of mortality, impacting approximately 600 million individuals globally, with four million dying prematurely from these diseases. Compared to the results obtained in 1990, the morbidity and mortality rates have increased by 39.8 and 18.0%, respectively (1). Chronic obstructive pulmonary disorder (COPD), asthma, acute respiratory infections (especially the coronavirus disease 2019 [COVID-19] pandemic), and lung cancer are the most common pulmonary diseases which together place a significant financial burden on global public health. Numerous observational studies and meta-analyses have shown that socioeconomic status is closely linked to pulmonary disease-related morbidity (2). For example, one repeated cross-sectional analysis of 160,495 participants spanning half a century in America reported that socioeconomic disparities in pulmonary health have persisted, and potentially worsened over the past six decades. Socioeconomic status can serve as an independent determinant of pulmonary health (3), a perspective which was also supported by independent studies conducted in China and Europe (4, 5). Nevertheless, observational studies have limitations, such as the absence of randomization, potential confounding factors, challenges in controlling variables, and an inability to establish causality due to unaccounted factors that may bias the outcomes. Thus, additional research is necessary to gain a deeper understanding of this relationship.

Mendelian randomization (MR) utilizes valuable genetic variants, such as single nucleotide polymorphisms (SNPs), as instrumental variables (IVs) to evaluate the causal effects between modifiable, non-genetic exposure factors and genetic susceptibility to diseases. This type of analysis is grounded in Mendel’s law of inheritance, which explains the random allocation of genetic variants during meiosis (6). In the absence of randomized controlled trials (RCTs), MR studies offer an alternative approach for causal inference, as genetic variants are randomly assigned during meiosis, thus mimicking the randomization in the RCT process. Compared to traditional observational studies, the main advantage of MR studies is that they are less likely to be influenced by unmeasured confounding factors as genetic variants are identified at the time of conception (7, 8). MR studies have successfully elucidated causal relationships between behavioral exposure, education, socioeconomic conditions, and diseases (9–11). Therefore, the aim of this study was to identify a bidirectional causal relationship between household income and genetic susceptibility to common pulmonary diseases using MR.

Previous epidemiological studies have demonstrated that socioeconomic status has a significant impact on pulmonary diseases (25). Given its integral nature as an aspect of socioeconomic status, household income status has also consistently been linked to pulmonary diseases. Nevertheless, the underlying causal relationship remains unclear. To the best of our knowledge, this study is the first to investigate the causal relationship between household income status and pulmonary diseases using a bidirectional two-sample MR approach. Our findings suggest that individuals with a higher household income tend to have a lower risk of developing COPD, asthma, and lung cancer. Additionally, a reverse MR analysis did not indicate any reverse causal relationship between pulmonary disease and household income status.

Our findings are supported by accumulating evidence from both cohort studies and meta-analyses. Adeloye et al. reported that more than three-quarters of global COPD cases occur in low- and middle-income countries (26). Meanwhile, a multicenter study with 11,042 participants directed by Matthew Grigsby revealed that the prevalence of COPD was negatively associated with monthly household income status (OR = 0.96 per category, 95% CI = 0.93–0.99) (27). Moreover, Pakhale et al. reviewed the association between socioeconomic status and COPD morbidity in Ottawa. They showed that the population with a lower household income had a significantly higher COPD prevalence than the average citizen (28). Similarly, Yan Borné et al. suggested that, in Sweden, low annual income is a risk factor for COPD (hazard ratio [HR] = 2.23; 95% CI = 1.97–2.53, p < 0.001) (29). Asthma is another threatening respiratory disease affecting all age groups, particularly children (30). Multiple observational studies have concluded that populations with inferior family income status are at an increased risk of suffering from asthma (31–33). In addition, lung cancer is an increasing problem in developing countries because of increasing smoking trends, high incidence of air pollution, lack of awareness and screening, delayed presentation, and late diagnosis (34). In this study, we identified low-income status as a risk factor for lung cancer. This viewpoint concurs with the conclusions drawn by Orlewska et al. in Poland (35) and Fabian Tetzlaff et al. in Germany (36). Additionally, a prior study on the geographical distribution of mortality in urban areas in Spain revealed that areas with high mortality from COPD and lung cancer often coincided with low-income neighborhoods (37). Together, the results of these studies show that household income status and the poor living environment which occurs as a consequence are risk factors for respiratory diseases, such as COPD, asthma, and lung cancer.

Several pathological mechanisms may explain the association between household income and genetic susceptibility to pulmonary diseases. First, it is well known that air pollution and smoking are essential risk factors for pulmonary diseases. Populations with inferior household income status and living standards in low-income countries may not only be susceptible to poor living conditions, but may also be more likely engage in unhealthy lifestyle behaviors such as smoking. Gaffney et al. reported that, in the United States, current/former smoking rates in the highest income quintile decreased by ~50% from 1971 to 2018, while the rates in the lowest income quintile remained largely unchanged at an alarming level of ~60% (3). Secondly, populations with lower household incomes are more likely to face deficiencies in nutrients, such as high-quality protein, fresh fruits and vegetables, dietary fiber, vitamins, and micronutrients. These nutrients are closely linked to immune system function in vivo, particularly during pregnancy and childhood (38–41). Finally, low-income populations are less likely to have access to healthcare services and more likely to lack health consciousness, which may result in respiratory diseases that persist for a long time. Gaffney et al. concluded that, even though the uninsured rate among adults with asthma in the US decreased from 19.4 to 9.6% (adjusted 9.27 percentage points; 95% CI = 7.1–11.5%) from 1997 to 2018, the proportions delaying or foregoing medical care because of cost or going without medications did not improve. Meanwhile, in the same study, a similar trend was also reported in patients with COPD (42).

Although this study has provided valuable scientific insights, however, there are several limitations that need to be addressed. Firstly, the GWAS datasets utilized in the MR analysis primarily including individuals of European descent, suggesting that the findings may not be fully applicable to other ethnic groups. Secondly, the biological mechanisms of SNPs and their impact on human susceptibility to respiratory diseases require further exploration. Finally, the current MR study did not include a sub-group analysis for populations known to be at increased risk of COPD, asthma, and lung cancer. By incorporating such an analysis, we could enhance the practical utility of the study by obtaining a more comprehensive understanding of how household income affects diverse population subgroups. This, in turn, could facilitate the development of more targeted policies and support measures.

Overall, the results of this bidirectional MR study demonstrated that individuals with higher household income exhibit a reduced risk of genetic predisposition to COPD, asthma, and lung cancer. These findings highlight the need to include household income disparities in medical reimbursement policies, and to prioritize efforts to enhance equal access to and availability of medical services for individuals in low-income households.

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

The requirement of ethical approval was waived for the studies involving humans because the variable genetic information involved in this study was extracted from the Integrative Epidemiology Unit (IEU) GWAS database (12) (https://gwas.mrcieu.ac.uk/), which is a publicly available GWAS summary database. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in these studies.

HX: Conceptualization, Writing – original draft. HD: Writing – original draft, Data curation. YW: Data curation, Writing – original draft. YY: Conceptualization, Supervision, Writing – review & editing. XZ: Methodology, Project administration, Writing – review & editing.