Eosinophilia, asthma, NERD and the use of oral corticosteroids predict uncontrolled chronic rhinosinusitis with nasal polyps after surgery.

BACKGROUND: Severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenging condition to treat. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) has the following criteria when considering biological therapy for severe uncontrolled CRSwNP: eosinophilia, need for oral corticosteroids (OCS), symptom score, loss of sense of smell and co-morbid asthma. OBJECTIVE: This study aimed at finding associations of baseline factors with uncontrolled CRSwNP after endoscopic sinus surgery (ESS). METHODS: Electronic health record data of CRSwNP patients (N = 137) undergoing ESS in 2002-17 were used. Endpoints of uncontrolled CRSwNP were revision ESS, purchased OCS and antibiotic courses during follow up. Baseline factors were chosen based on EPOS2020 and the data available: nasal polyp (NP) eosinophilia, peripheral blood eosinophilia, co-existing asthma and/or non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD), need for OCS during the previous year, previous ESS, endoscopic NP score, and Lund-Mackay score of sinus computed tomography scans. RESULTS: During the follow-up of 10.1 ± 3.1 (mean ± standard deviation) years, 35 (25.5%) individuals underwent revision ESS. The best predictive model was obtained by a sum of baseline (1) blood eosinophilia ≥ 250 cells/≥l and/or NP eosinophilia ≥ 30% (Eos), (2) asthma/NERD, and (3) ≥ 1 OCS/year. It was significantly associated with revision ESS, purchased doctor-prescribed OCS and antibiotic courses during follow-up. CONCLUSIONS: We identified similar predictive variables for uncontrolled CRSwNP that are used in the EPOS2020 indications of biological therapy, thus suggesting that these estimates are usable in clinical practice.

Factors affecting upper airway control of NSAID-exacerbated respiratory disease: A real-world study of 167 patients.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (N-ERD) is a triad with asthma, chronic rhinosinusitis with nasal polyps, and NSAID intolerance. Uncontrolled N-ERD forms a major public health problem due to frequent and difficult-to-treat exacerbations and/or requiring putatively frequent endoscopic sinus surgeries (ESS). Our aim was to study factors affecting control of N-ERD. METHODS: Retrospective patient record data (patient characteristics, prior sinus surgeries, follow-up data in 2020) from 167 N-ERD patients undergoing consultation at three tertiary hospitals from 2001 to 2017 was used. Outcome measurements reflecting uncontrolled N-ERD were revision ESS, corticosteroids/biological therapy, and antibiotic courses during 2016-2020. Associations were analyzed by using nonparametric tests, Cox's proportional hazard, and binary logistic regression models. RESULTS: Nasal polyp eosinophilia increased the risk of revision surgery during the follow-up (adjusted hazard ratio [aHR] 3.21, confidence interval 1.23-8.38). Also baseline oral corticosteroids (OCS; HR, 1.73, 1.04-2.89) and baseline surgery without total ethmoidectomy increased the risk of revision ESS (HR, 2.17, 1.07-4.42) in unadjusted models. In addition, both baseline OCS (adjusted odds ratio [aOR] 2.78, 1.23-6.26) and a history of ≥4 previous ESS (aOR, 2.15, 0.98-4.70) were associated with the use of OCS/biological therapy during the follow-up, but not with high number of antibiotics. CONCLUSIONS: Nasal polyp eosinophilia, baseline OCS, and a history of recurrent ESS predict uncontrolled N-ERD. These factors might be clinically useful in risk-estimation of uncontrolled disease and for organizing follow-ups. Prospective cohort studies with larger sample size are needed to further study the factors affecting the upper airway control of N-ERD.

High Discontinuation Rates of Peroral ASA Treatment for CRSwNP: A Real-World Multicenter Study of 171 N-ERD Patients.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) exacerbated respiratory disease (N-ERD) consists of chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, and NSAID intolerance. Acetylsalicylic acid treatment after desensitization (ATAD) is a treatment option for uncontrolled N-ERD. OBJECTIVE: To evaluate peroral ATAD's long-term effectiveness on CRSwNP disease control. METHODS: The retrospective data (patient characteristics, sinus surgeries before ATAD, ATAD, follow-up data [2019]) were collected from patient records of 171 patients with N-ERD (102 ATAD patients, 69 controls with CRSwNP+N-ERD without ATAD) who underwent tertiary hospital consultation from 2001 to 2017. Outcome measurements were ATAD discontinuation, revision sinus surgery, and corticosteroid and antibiotic courses for airway infections during 2016-2019. Associations were analyzed by survival and nonparametric methods. RESULTS: The ATAD group had more tissue eosinophilia, symptoms, and sinus surgeries before ATAD than others. The ATAD discontinuation rate was 63%, independent of ATAD dose or duration, usually due to side effects. Compared with the N-ERD group without ATAD, ATAD (mean duration, 2.9 years) did not affect the revision endoscopic sinus surgery rate (P = .21, by the log-rank test) or the number of peroral corticosteroid courses per year (P > .05, by the Mann-Whitney U-test) during the follow-up (mean, 7.6 years) despite the dose or duration of ATAD. CONCLUSIONS: The discontinuation rate of ATAD was high (63%), and ATAD did not affect revision sinus surgery rate nor the need of peroral corticosteroids during follow-up. However, the remaining 37% of the ATAD group did continue the treatment, indicating that they may have benefited from ATAD.

Impaired nasal breathing may prevent the beneficial effect of weight loss in the treatment of OSA.

BACKGROUND: Weight loss is considered an effective treatment for obstructive sleep apnoea (OSA) in overweight patients. Some patients, however, do not benefit from weight loss. It has been postulated that nasal obstruction may act as an independent risk factor for OSA. OBJECTIVE: The aim of our study was to evaluate whether impaired nasal airflow might explain the missing effect of weight reduction on OSA. METHODOLOGY: Fifty-two overweight adult patients with mild OSA were recruited. After the 12-month lifestyle intervention, all patients who achieved more than 5% weight loss were divided into two groups based on whether they still had OSA or not. Change in nasal resistance measured by rhinomanometer and AHI were the main outcome variables. RESULTS: A total of 26/52 patients achieved 5% weight reduction. Of those 26 patients, 16 were objectively cured from OSA and 10 patients did not benefit from weight loss. Nasal resistance reduced significantly more in patients who had been cured from OSA. Smoking had a negative impact on both nasal resistance and improvement of AHI. CONCLUSIONS: Impaired nasal breathing and smoking may prevent the beneficial effects of weight reduction in the treatment of OSA.

Sustained improvement in mild obstructive sleep apnea after a diet- and physical activity-based lifestyle intervention: postinterventional follow-up.

BACKGROUND: Obesity is the most important risk factor for obstructive sleep apnea (OSA). Weight-reduction programs have been observed to represent effective treatment of overweight patients with OSA. However, it is not known whether beneficial changes remain after the end of the intervention. OBJECTIVE: The aim of the study was to assess the long-term efficacy of a lifestyle intervention based on a healthy diet and physical activity in a randomized, controlled, 2-y postintervention follow-up in OSA patients. DESIGN: Eighty-one consecutive overweight [body mass index (in kg/m(2)): 28-40] adult patients with mild OSA were recruited. The intervention group completed a 1-y lifestyle modification regimen that included an early 12-wk weight-reduction program with a very-low-calorie diet. The control group received routine lifestyle counseling. During the second year, no dietary counseling was offered. Change in the apnea-hypopnea index (AHI) was the main objective outcome variable, and changes in symptoms were used as a subjective measurement. RESULTS: A total of 71 patients completed the 2-y follow-up. The mean (± SD) changes in diet and lifestyle with simultaneous weight reduction (-7.3 ± 6.5 kg) in the intervention group reflected sustained improvements in findings and symptoms of OSA. After 2 y, the reduction in the AHI was significantly greater in the intervention group (P = 0.049). The intervention lowered the risk of OSA at follow-up; the adjusted odds ratio for OSA was 0.35 (95% CI: 0.12-0.97; P = 0.045). CONCLUSION: Favorable changes achieved by a 1-y lifestyle intervention aimed at weight reduction with a healthy diet and physical activity were sustained in overweight patients with mild OSA after the termination of supervised lifestyle counseling. This trial was registered at clinicaltrials.gov as NCT00486746.

The activation of the inflammatory cytokines in overweight patients with mild obstructive sleep apnoea.

It is widely accepted that obstructive sleep apnoea (OSA) is linked with cardiovascular diseases. The relationship is complex and remains still poorly understood. The presence of chronic systemic inflammation has been connected with pathogenesis of both OSA and cardiovascular diseases. While atherogenesis is believed to be a process of many years, little is known about the potential impact of the largest OSA subgroup, mild OSA, on the development of cardiovascular diseases. The aim of the present study was to assess whether untreated mild OSA is associated with an activation of inflammatory cytokine system. The adult study population consisted of two groups: 84 patients with mild OSA [apnoea-hypopnoea index (AHI) 5-15 h(-1)] and 40 controls (AHI <5 h(-1)). Serum concentrations of pro- and anti-inflammatory cytokines were measured before any interventions. After adjustments for age, sex, body mass index, fat percentage, most important cardiometabolic and inflammatory diseases, and non-steroidal anti-inflammatory medication, the mean level of tumour necrosis factor-alpha was significantly elevated (1.54 versus 1.17 pg mL(-1), P = 0.004), whereas the level of interleukin-1 beta (IL-1 beta) was reduced (0.19 versus 0.23 pg mL(-1), P = 0.004) in patients with mild OSA compared with controls. The concentrations of the protective anti-inflammatory cytokines, interleukin-10 (1.28 versus 0.70 pg mL(-1), P < 0.001) and interleukin-1 receptor antagonist (478 versus 330 pg mL(-1), P = 0.003) were elevated in the OSA group. The concentrations of C-reactive protein increased, but IL-1 beta decreased along with the increase of AHI. Mild OSA was found to be associated not only with the activation of the pro-inflammatory, but also with the anti-inflammatory systems.

Lifestyle intervention with weight reduction: first-line treatment in mild obstructive sleep apnea.

RATIONALE: Obesity is the most important risk factor for obstructive sleep apnea (OSA). However, although included in clinical guidelines, no randomized controlled studies have been performed on the effects of weight reduction on mild OSA. OBJECTIVES: The aim of this prospective, randomized controlled parallel-group 1-year follow-up study was to determine whether a very low calorie diet (VLCD) with supervised lifestyle counseling could be an effective treatment for adults with mild OSA. METHODS: Seventy-two consecutive overweight patients (body mass index, 28-40) with mild OSA were recruited. The intervention group (n = 35) completed the VLCD program with supervised lifestyle modification, and the control group (n = 37) received routine lifestyle counseling. The apnea-hypopnea index (AHI) was the main objectively measured outcome variable. Change in symptoms and the 15D-Quality of Life tool were used as subjective measurements. MEASUREMENTS AND MAIN RESULTS: The lifestyle intervention was found to effectively reduce body weight (-10.7 +/- 6.5 kg; body mass index, -3.5 +/- 2.1 [mean +/- SD]). There was a statistically significant difference in the mean change in AHI between the study groups (P = 0.017). The adjusted odds ratio for having mild OSA was markedly lowered (odds ratio, 0.24 [95% confidence interval, 0.08-0.72]; P = 0.011) in the intervention group. All common symptoms related to OSA, and some features of 15D-Quality of Life improved after the lifestyle intervention. Changes in AHI were strongly associated with changes in weight and waist circumference. CONCLUSIONS: VLCD combined with active lifestyle counseling resulting in marked weight reduction is a feasible and effective treatment for the majority of patients with mild OSA, and the achieved beneficial outcomes are maintained at 1-year follow-up.