Asthma and Obstructive Sleep Apnea: Clinical and Pathogenic Interactions

Abstract

Asthma and obstructive sleep apnea (OSA) are among the most prevalent chronic human diseases of the 21st century. They share several risk and aggravating factors such as obesity, smoking, gastroesophageal reflux, sinonasal disease or upper airway involvement, systemic inflammation, etc. Although the association between OSA and chronic obstructive pulmonary disease or "overlap syndrome" is better known and characterized, the association of asthma and OSA or "alternative overlap syndrome" is less clearly defined and understood. Nevertheless, their coexistence has synergistic effects on patient symptoms, response to therapy, and general outcomes. Taxonomically, asthma and OSA are syndromically defined entities that are quite heterogeneous, being characterized by a plethora of clinical phenotypes. The complex interactions between these conditions should take into account more specific etiopathogenic mechanisms or distinct disease endotypes. The potential clinical, pathogenic, and therapeutic significance of the disease endotypes is still emerging and needs further evaluation. We present here a review on the bidirectional relationships between asthma and OSA, including their clinical, pathophysiologic, and therapeutic connections. Furthermore, we propose here to look at these interactions beyond the development of comprehensive inventories of genotypes, clinical and pathophysiologic phenotypes, but in the larger context of obstructive lung and airway disorders, with the goal to reassess meaningful syndromes based on natural history and predictable patient outcomes, which will help us better stratify therapy in an era of personalized medicine.

Asma bronquial y síndrome de apnea/hipopnea obstructiva del sueño: ¿el nuevo “síndrome de superposición alternativo”?

“…En el Community Health Respiratory Survey en el Reino Unido, se encontró que personas con asma de todas las edades y pesos roncaban con mayor frecuencia que los controles (29% vs. 9%). Así mismo, en los europeos, el autorreporte de ronquido habitual y apnea fue significativamente más frecuente en personas con asma comparados con los controles sin asma (14% vs. 9% y 3% vs. 1%, respectivamente), independientemente de su edad, peso corporal, sexo o tabaquismo (4).…”

“…A pesar de que los fenotipos asma-obesidad y endotipos han sido descritos recientemente, sería interesante estudiar de manera sistemática la contribución de los trastornos respiratorios del sueño a todos ellos (4).…”

Complicating effects of obstructive sleep apnea syndrome on the severity of adult asthma

“…The nocturnal upper airway stenosis and nocturnal hypoxia of OSAS have the potential to aggravate BA symptoms directly. In addition, TNF-a, interleukin-6, vascular endothelial growth factor, leptin, and other inflammatory mediators and adipokines produced during OSAS are believed to induce airway changes and sensitization, indirectly aggravating BA and making it intractable to treatment (2,4,5). Several epidemiologic studies have shown that BA patients are more likely than the public as a whole to have OSAS (6)(7)(8), thus suggesting an interaction between BA and OSAS.…”

“…Several epidemiologic studies have shown that BA patients are more likely than the public as a whole to have OSAS (6)(7)(8), thus suggesting an interaction between BA and OSAS. In OSAS patients who develop BA, the lower airway stenosis due to BA increases the treatment intractability of OSAS, and BA-associated allergic rhinitis and steroid treatment may further exacerbate OSAS (2,4). Other studies, however, have failed to identify a direct interaction between OSAS and BA (9), and a clear consensus regarding the effects of OSAS and BA on each other has yet to be reached.…”

Anti-CTGF Single-Chain Variable Fragment Dimers Inhibit Human Airway Smooth Muscle (ASM) Cell Proliferation by Down-Regulating p-Akt and p-mTOR Levels

“…Asthma is considered an inflammatory disease of the airway that responds poorly to current therapies and affects more than 300 million individuals worldwide [1] . Severe persistent asthma can result in structural changes in the airway, such as thickening of the basement membrane, airway smooth muscle (ASM) hyperplasia and/or hypertrophy, changes in the extracellular matrix (ECM) composition and an increase in the number of blood vessels, which are collectively referred to as airway remodeling [2] – [5] .…”