Discussion
To the best of our knowledge, the present study is first to examine the prevalence of asthma within a patient population with radiologically confirmed HH. Innovatively, the present study also aimed to assess disease severity in patients with a known diagnosis of asthma, and to conduct early screening for respiratory symptoms in patients with HH and no known respiratory disease. The present study provides a comprehensive perspective on the prevalence, severity and early screening of asthma, and other respiratory conditions in patients with radiologically confirmed HH.
The clinical relevance of HH is well-established, given its implication in GERD, its association with interstitial lung diseases and micro-aspirations (12,13), and its tendency to decrease quality of life (14). However, little is known about the prevalence of HH and its association with asthma. This is, at least in part, due to the fact that asymptomatic individuals are rarely subjected to standard HH tests, such as endoscopy, manometry, or esophago-gastro-duodenal transit.
The present study reported a 7.53% prevalence of radiologically detected HH, including the diaphragmatic hiatus, in computed tomography scans analyzed for 17,374 patients, over the period from January, 2020 to May, 2023. This finding aligns with the results of a study conducted by Rahman et al (15), which reported a similar prevalence of 8.8%.
The average age of the patients with HH was 67 years (interquartile range, 63-83), a result consistent with a meta-analysis including data from seven studies (16). That meta-analysis revealed a significant association with an age >50 years and the occurrence of HH. This association may be attributed to the decreased elasticity of the phrenoesophageal ligament, responsible for anchoring the esophagus to the diaphragm and potentially contributing to increased susceptibility to the development of HH.
Furthermore, 280 (61.81%) patients were female, a distribution consistent with the results of another study (17), suggesting a potential female predilection among patients with HH. In the present our study population, 3.53% of the patients with HH had undergone surgical intervention for HH repair, a percentage higher than reported in comparable studies (18). This may be attributed to factors, such as an increased awareness of surgical interventions for HH, evolving surgical techniques, or higher severity of hernias prompting surgical management in this particular cohort.
Collectively, these findings underscore the critical role of HH as a structural contributor to GERD (19,20).
In the present study, it was observed that 67 out of the 453 patients with HH had asthma (14.79%), previously diagnosed and managed clinically. Notably, this prevalence exceeds the global prevalence of asthma in the general population, which was estimated at 3.57% in 2017(21), as well as the reported prevalence of physician-diagnosed asthma in Lebanon, reported at 6.7% (22). The elevated rates of asthma in patients with HH underscores a potentially higher prevalence of asthma among patients with HH, compared to global and national averages. This finding is consistent with that of another study where HH was more frequently observed in patients with asthma rather than asthma-free subjects (62 vs. 34%, P=0.02) (23). This observation is warranted to prompt medical attention and asthma screening in this patient subset.
Several explanations have been proposed to elucidate the association between asthma and HH-induced GERD. Pulmonary hyperinflation is common among patients with asthma. The descent of the diaphragm during pulmonary hyperinflation and increased respiratory effort results in a high-pressure gradient between the abdomen and thorax. This can lead to the herniation of the lower esophageal sphincter into the thorax, impairing its barrier function. Consequently, this may allow increased gastric reflux in asthmatics with hyperinflation (24).
Additionally, certain asthma medications attempting to reduce hyperinflation may worsen acid reflux. β-agonists have been shown to reduce the tone of the lower esophageal sphincter in a dose-dependent manner (25). This raises the possibility of a vicious cycle where asthma symptoms caused by GERD lead to the increased use of bronchodilators, exacerbating GERD symptoms.
Other pathways may shed light on the potential mechanisms by which GERD may cause or exacerbate airway obstruction in patients with asthma. Firstly, repetitive GERD-related acid micro-aspiration into the larynx and upper airways can exacerbate respiratory conditions, including asthma and chronic obstructive pulmonary disease, according to a previous histological lung analysis in a rat model of surgically-induced GERD (26). Secondly, reflux episodes can trigger an esophago-bronchial vagal reflex and increased bronchial reactivity, potentially leading to bronchoconstriction. A previous study involving intra-esophageal acid infusions demonstrated a decrease in peak expiratory flow even without signs of micro-aspiration, implying vagally-mediated reflex involvement (27). Of note, these broncho-constrictive reactions were not dependent on esophageal mucosal inflammation or micro-aspiration. These molecular findings clarify the complex link between asthma and GERD induced by HH.
Using the GINA assessment of asthma control, the present study revealed distinct trends in the severity of asthma among the study participants. Specifically, 23.88% had ‘well-controlled’ asthma symptoms, 34.33% had ‘partially controlled’ asthma, and 41.79% had ‘uncontrolled’ asthma symptoms. This distribution is in contrast with the results of the PRISMA study (28), a large cross-sectional study involving 2,853 adults with asthma, where up to 64.4% of patients had controlled asthma, 15.8% had partially controlled asthma and 19.8% had uncontrolled asthma. Similarly, another recent study conducted in the general population (29), reported that uncontrolled asthma was present in 26% and partially controlled asthma in 22.9% of patients.
In the present study, it was reported that patients with HH appeared to have a higher prevalence of ‘uncontrolled’ and ‘partially controlled’ asthma. This may be due to the potential impact of HH on respiratory function, leading to an increased asthma severity, or underlying common mechanisms contributing to both conditions.
In the present study, the frequency of respiratory symptoms (outside of an asthma diagnosis) was reported using a previously published questionnaire that evaluated the status of occupational asthma in a cohort of workers (30). The findings obtained herein indicated notable differences between patients diagnosed with HH and those with untreated asthma-like symptoms described in the worker cohort in the previous study (30). Chest wheezing (13.74 vs. 26.20%) and waking up due to coughing (13.99 vs. 51.50%) were less common in the population of patients with HH compared with the worker population. However, the patients in the present study reported a higher prevalence of symptoms, such as waking up due to shortness of breath (22.54 vs. 11.20%) and asthma attacks (1.81 vs. 0.6%). These differences might be due to inherent bias in the study sample selection. The overestimation of respiratory symptoms in the worker population may be attributed to variations in age and occupational exposure. Specifically, the worker population was younger than the average age of 67 years reported in the present study and environmental factors specific to the workplace could play a role in exacerbating respiratory symptoms.
The evaluation of GERD symptoms and asthma among patients with HH indicated a higher rate of asthma among patients with GERD symptoms (16.85%) compared to those without (11.49%); however, this difference did not reach statistical significance (P-value=0.1). In a previous study on >100,000 patients, patients with GERD were 1.51-fold (1.43-1.59) more likely to suffer from asthma than patients without GERD (31).
Patients undergoing treatment for GERD with PPIs or other anti-reflux medications had a higher prevalence of asthma (17.48%) than those not receiving anti-acid treatment (10.18%), with a statistically significant P-value of 0.03. This aligns with the findings of a broader research (32), where the overall incidence of asthma was 1.58-fold higher in patients treated with PPIs than those not receiving PPIs.
While the present study did not detect a significant sex predilection for asthma presentation in patients with HH, previous studies have suggested that in adulthood, females exhibit increased an prevalence and severity of asthma (33-35).
In order to manage their GERD symptoms, patients with HH are frequently advised to make certain lifestyle changes, such as losing weight, changing their diet and sleeping at an angle. Controlling asthma may be indirectly affected by these lifestyle modifications. For example, losing weight can help asthmatic outcomes by enhancing lung function and decreasing systemic inflammation. However, the stress of dealing with several chronic illnesses (HH, asthma and GERD) may cause patients to adhere to these lifestyle treatments less than optimally, particularly if they prioritize one ailment over the others.
Finally, it is important to recognize the psychological toll that having both asthma and HH can have. The symptoms of both conditions, fatigue, chest discomfort and shortness of breath, can overlap and result in severe anxiety, which may lead to a psychosomatic amplification of symptoms and worsen asthma severity, as well as the perceived impact of HH on daily life. Including mental health services in the treatment plan for these patients may help lessen this burden and enhance symptom control.
In summary, although there are clear physiological connections between HH and asthma, patients with both conditions require a comprehensive approach to care that takes into account not only pharmacological interventions, but also lifestyle, psychosocial and even neurogenic aspects. The knowledge gained from this research opens the door to more complex, interdisciplinary approaches to treatment, guaranteeing that patients get all-encompassing assistance for both their digestive and respiratory systems.
As regards, limitations and bias, firstly, the present study relied on a retrospective design, which may have introduced biases related to data collection. A limitation of the present study is the variability in patient data collection over time, as the health status of patients from earlier years, such as 2020, may have evolved by the final analysis in 2023. Disease progression in conditions such as HH and asthma could mean that more recent data could better reflect current health trends. Additionally, in the absence of a control group (patients without HH evaluated for asthma or other respiratory conditions), a direct association between the prevalence of asthma and the presence of HH cannot be established. Comparisons had to be primarily made with data from the literature. In addition, the present study did not stratify the results based on potential confounders, such as comorbidities, age and smoking status; which limits the generalizability of the results.
In conclusion, the present study uniquely identifies a significantly higher prevalence of asthma (14.79%) among patients with HH compared to global asthma prevalence rates. Notably, 41.79% of asthmatic patients demonstrated an inadequate control of their condition, indicating that asthma severity in this population may be underrecognized and undertreated. The findings from the present study suggest that HH may play an underappreciated role in respiratory health, warranting increased clinical vigilance and a proactive approach to diagnosing and managing respiratory comorbidities in this population.
In clinical practice, while the presence of HH should be considered when evaluating patients with difficult-to-control asthma, further evidence is required to support their routine identification as a key factor in asthma management. Longitudinal studies with more robust data and extended follow-up are necessary to confirm the potential progression of asthma in patients with HH and to evaluate the impact of specific interventions on respiratory outcomes. Additionally, more detailed research into the underlying mechanisms linking HH and asthma may shed light on potential pathways for targeted therapies and refined treatment approaches for these patients.