Table 2.
Included studies from the review.
| First Author, Year | Aim of the Study | Subjects and Methods | Inhaled Corticosteroid | Asthma | OSA and SDB | Conclusion |
|---|---|---|---|---|---|---|
| ADULTS | ||||||
| Teodorescu M, et al., 2009 [44] | Risk Factors Associated with Habitual Snoring and OSA Risk in Asthmatic Patients | Survey of 284 asthmatics (age 46 ± 13 range 18–75 years). N.143/284 (50%) had SDB or met the criteria for high OSA risk. Valutazione SDB: Self-Reported OSA, Symptom, SA-SDQ |
Use of ICSs: n.201 (82%): low dose 31, medium dose 87, and high dose 83. No. 65 patients with grade 1 asthma: n.13 (20%) with high doses of ICSs; n.20 (31%) without ICSs. N.77 patients with grade 4 asthma => n.12 (16%) non-use of ICSs; n.43 (56%) high doses of ICSs. |
Recent spirometry data collected to assess asthma severity step: predictor of habitual snoring in 244 asthma patients was asthma severity step, aOR 1.22 (95% C.I. 0.94–1.60), p = 0.14. Predictor of high-risk OSA in 244 asthma patients was asthma severity step aOR 1.59 (95% C.I. 1.23–2.06), p < 0.001. |
+129% risk of OSA with low-dose ICSs (OR, 2.29; C.I. 95% = 0.66–7.96); +267% with mid-dose ICSs (OR, 3.67; C.I. 95% = 1.34–10.03); and +443% with high-dose ICSs (OR, 5.43; 95% C.I. = 1.96–15.05) compared to no use of ICSs. Dose-dependent relationship between habitual snoring and ICS dose (overall p = 0.004). Dose-dependent relationship between high OSA risk and ICS dose (overall p < 0.001). |
Increased risk of OSA associated with ICS use. Proportional increase in risk based on the dosage of ICSs used. |
| Teodorescu M, et al., 2014 [45] | Effects of Orally Inhaled FP on UAW During Sleep and Wakefulness in Asthmatic Subjects | Prospective, single group and center study. Baseline: 18 participants with asthma (age 25.9 ± 6.3 years; range 18–75 years). 16-week ICS (FP) treatment. Asthma duration: 14.4 ± 10.2 years. Pcrit; MRI (fat fraction and volume around the upper airway). Valutazione SDB: Self-Reported OSA Symptom, SA-SDQ |
High dose inhaled FP (1760 mcg/day). Dose adherence of FP was 91.2% ± 1.7%. |
FEV1% pretreatment 88.8 ± 1.9; post treatment 94.1 ± 0.1 (p = 0.001). | AHI baseline (events/h) = 1.2 ± 2.0, improved n.8 (0.51 ± 0.48), unchanged n.8 (1.64 ± 0.79), and worsened n.2 (2.40 ± 2.40). SA-SDQ baseline score = n.18 (21.2 ± 3.9), improved no. 8 (19.38 ± 0.98), unchanged n.8 (22.00 ± 1.40), and worsened No. 2 (25.00 ± 4.00). Pcrit: improved n.8 (−8.16 ± 1.36), unchanged n.8 (−8.51 ± 2.18), and worsened n.2 (−7.35 ± 0.85). Changes in tongue strength with fluticasone inhaled treatment, in the anterior (p = 0.02) and posterior (p = 0.002) positions. |
High-dose FP led to improvements in lung function (FEV1%). Improved Pcrit in some participants. No significant impact on AHI after FP treatment. No reduction in overall AHI. High-dose FP appears to be associated with an increase in fat fraction and total fat volume in surrounding upper airway structures. |
| Shen TC, et al., 2015 [46] | Factors Associated with Habitual Snoring and SDB Risk in Asthmatic Patients | Retrospective cohort study. With asthma: 38,840 (age 52.8 ± 18.1 years; range 20–≥ 65 years). Asthma-free: 155,347 (age 53.3 ± 18.0 years; range 20–≥ 65 years). Follow-up period: with asthma 6.95 ± 3.33 years; control 6.51 ± 3.44 years. SDB Rating: PSG |
OSA risk ratio among asthma patients based on different treatments. ICS 11,214 (15.3 per 1000 persons/year). No ICS 13,792 (10.6 per 1000 persons/year). |
aHR +2.51 (95% C.I. (1.61, 2.17) of OSA in the asthmatic cohort compared to control (12.1 vs. 4.84 per 1000 person-years). OSA development during follow-up: aHR +1.87 (95% C.I. = 1.61–2.17) for the asthma cohort compared to the non-asthma cohort. |
OSA in asthma patients: Non-steroid aHR 1 (reference). Inhaled steroid aHR 1.33 (95% C.I. 1.01–1.76). |
Overall incidence of OSA is higher in the asthmatic cohort than in the control cohort. ICS appears to be associated with an even higher incidence of OSA among asthmatic patients. |
| Henao MP, et al., 2020 [48] | Effects of ICS on the Diagnosis of OSA, with Sub-Analysis by Particle Size of ICSs. | Cohort study. 29,816 asthmatics (age 42.8 ± 21.1 years). ACT and PFT [A diagnosis of SDB was determined using ICD-9 or ICD-10 codes]. |
Higher likelihood of OSA in ICS users with standard particle sizes (aOR +1.56, 95% C.I. 1.45–1.69) than in non-users. There was no increased risk of OSA in users of ICSs with extra-fine particles compared to asthmatics who did not use ICS (aOR 1.11, 95% C.I. 0.78–1.58). |
Patients with uncontrolled asthma showed a higher likelihood of receiving a diagnosis of OSA. ACT score (aOR +1.60, 95% C.I. 1.32–1.94) among n.1380 uncontrolled asthma versus 3288 controlled asthma. PFT score (aOR +1.45, 95% C.I. 1.19–1.77) among 1229 uncontrolled and 1199 controlled asthma. ICS users were more likely to have OSA, regardless of asthma control (aOR 1.58, 95% C.I. 1.47–1.70). |
Probability of having a diagnosis of OSA with normal-sized particle ICSs (OR 1.55, 95% C.I. 1.11–2.16) compared to those with extra-fine particles. Increased odds of having OSA in BMI patients ≥ 25 users of normal-sized-particle ICSs compared to users of extra-fine particles (aOR 1.70, 95% C.I. 1.15–2.50). Increased odds of receiving OSA diagnosis in male BMI ≥ 25 users of normal-sized-particle ICSs compared to extra-fine particles (aOR 2.45, 95% C.I. 1.22–4.93). |
Compared to non-users of ICSs, there is an increased risk of OSA among users of ICSs with standard-sized particles. No increased risk of OSA was observed among users of ICSs with extra-fine particles. Patients with PCA showed a higher likelihood of OSA. The association between ICSs and OSA might vary based on asthma control and individual patient characteristics, such as BMI. |
| Ng SSS, et al., 2018 [47] | cPAP Effect on: Asthma Control, Airway Responsiveness, Daytime Sleepiness, and Health Status in Asthmatic Patients With Nocturnal Symptoms and OSAS | Prospective, randomized controlled trial. Baseline: 122 asthmatic subjects (≥18 years; age 50.5 ± 12.0 years). SDB Rating: PSG Patients with AHI ≥ 10 (n = 41). Patients with AHI < 10 (n = 81). CPAP group (n = 17) and control group (n = 20). |
Beclomethasone 500 μg or more per day within the last 3 months. Baseline. High-dose inhaled steroids 90.1%. Medium-dose inhaled steroids 9.9%, |
Baseline FEV1 (% predetto) 79.2 ± 20.5. No significant difference in the change in the ACT score between n.17 CPAP group 15.9 ± 2.6 vs. n.20 control group 21.7 ± 10.1 (p = 0.145). |
AHI correlates with BMI (r = 0.255, p = 0.008) and neck circumference (r = 0.247, p = 0.007). No significant difference in the change in the AHI score between n.17 CPAP group 19.1 ± 11.4 vs. n.20 control group 21.7 ± 10.1 (p = 0.474). |
Asthma control did not improve significantly despite taking at least a moderate dose of ICSs. This therapy may not be effective in improving asthmatic symptoms in patients with concomitant asthma and OSA. |
| CHILDREN | ||||||
| Ross KR, et al., 2012 [49] | Relationships Between Obesity, SDB, and Asthma Severity in Children | Prospective observational study, comparative study. Baseline: 108 (82%) asthmatic children (age 9.1 ± 3.4 years; range 4 to 18 years). Valutazione SDB: overnight finger pulse oximetry monitoring. No SDB (n.76) age 9.3 ± 3.4 years; SDB (n.32) age 8.7 ± 3.3 years. Predicted FEV1%: No SDB 98.7 ± 17.7; with SDB 90.9 ± 17.1. Associations between SDB, obesity, and asthma severity at follow-up. |
Severe asthma: children using high-dose ICSs alone or in combination with other drugs. Not severe asthma: low to moderate dose ICS. |
Asthma severity at 12-month follow-up: mild/mod (n.79) and severe (n.29). Asthmatic children with BMI z-score = 2 and SDB had a +6.7-fold risk (OR 1.74; 95% C.I.: 25.55) of having severe asthma compared to those without SDB. Children with asthma, BMI z-score 0, and SDB did not have an increased risk (OR +1.40; C.I. 95% 0.31–6.42) of having severe asthma compared to those without SDB. |
32 children (29.6%) with SDB. Children with prevalent SDB (OR 4.85, 95% C.I. 1.94–12.10) in severe asthma (55.2%) vs. mild/mod asthma (20.3%, p < 0.01). Children with SDB had an OR of 5.02 (95% C.I. 1.88 −13.44) to have severe asthma at follow-up (12 months), after adjustment for BMI z-score (p = 0.001). |
Children who are asthmatic, obese, and with SDB have a higher risk of severe asthma than those without SDB. Asthmatic, normal-weight, and SDB children using high doses of ICSs alone or in combination with other medications: there was no significant association between SDB and asthma severity. |
| Conrad LA, et al., 2022 [50] | Associations Between Sleep, Obesity, and Asthma in Urban Minority Children | Retrospective review of medical records; 448 children with asthma (ages 10.2 ± 4.1 years; range 7–18 years) who performed PSG. Association between spirometry variables, BMI, and PSG parameters, adjusting for asthma and anti-allergy medications. |
Inhaled steroids: obese asthmatics n.214 (74.1%) and normal weight asthmatics n.125 (81.2%) (p = 0.09). [Montelukast: obese asthmatics n.174 (60.2%) versus n.92 (59,7%), p = 0,92]. [Nasal steroids: asthmatics obese n.89 (30.8%) versus asthmatics normal weight n.44 (28.6%); p = 0.63]. |
FEV1: Obese asthmatics 83.1 ± 16.5, normal-weight asthmatics 86.4 ± 18.7 (p = 0.05). FEF25%–75%: Obese asthmatics 74.8 ± 26.5; normal-weight asthmatics 76.8 ± 28.2 (p = 0.4). |
289 obese asthmatics 5.9 ± 12.1 versus 154 normal-weight asthmatics 3.1 ± 5.7 (p = 0.009). | In obese asthmatic children, both ICSs and montelukast are associated with lower AHI. Neither ICSs nor montelukast are associated with sleep respiratory parameters in children with asthma of normal weight. |
Legend: AAE, acute asthma exacerbation; ACT, asthma control test scores; AHI, apnea–hypopnea index; aHR, adjusted HR; aOR, adjusted odds ratio; AT, adenotonsillectomy; ASA, acute status asthmaticus; ARERs, asthma-related emergency room visits; ARHs, asthma-related hospitalizations; BMI, body mass index; C.I., confidence interval; CPAP, continuous positive airway pressure; ER, emergency room; FP, fluticasone propionate; GER, gastroesophageal reflux; GINA, Global Initiative for Asthma 2020; HR, hazard ratio; HTN, systemic hypertension; ICSs, inhaled corticosteroids; LABAs, long-acting beta agonists; MRI, nuclear magnetic resonance; OCSs, Oral Corticosteroids; OSAS, obstructive sleep apnea syndrome; PCA, poorly controlled asthma; Pcrit, passive critical closing pressure; PFT, pulmonary function test; PSG, polysomnography; SABA, beta2-agonisti short-acting; SA-SDQ, Sleep Disorders Questionnaire; SDB, sleep-disordered breathing; UAW, upper airway collapsibility.