Association between undiagnosed obstructive sleep apnea and severe course of COVID-19: a prospective observational study.

PURPOSE: Obstructive sleep apnea (OSA) is associated with many long-term health consequences. We hypothesized that previously unrecognized and untreated OSA may be associated with more severe respiratory failure in hospitalized patients with COVID-19. METHODS: Patients hospitalized in the Pulmonology Department with confirmed COVID-19, University Hospital in Kraków, Poland, between September 2020 and April 2021 were enrolled. OSA screening questionnaires including Epworth Sleepiness Scale (ESS), STOP-BANG, Berlin questionaire (BQ), OSA-50, and No-SAS were completed. Polygraphy was performed after > 24 h without requirement for supplemental oxygen. RESULTS: Of 125 patients with median age of 61.0 years, 71% of whom were male. OSA was diagnosed in 103 patients (82%) and was categorized as mild, moderate, and severe in 41 (33%), 30 (24%), and 32 (26%), respectively. Advanced respiratory support was introduced in 85 patients (68%), and 8 (7%) patients eventually required intubation. Multivariable analysis revealed that increased risk of requirement for advanced respiratory support was associated with higher respiratory event index (OR 1.03, 95%CI 1.00 to 1.07), oxygen desaturation index (OR 1.05, 95%CI 1.02 to 1.10), and hypoxic burden (1.02 95% CI 1.00 to 1.03) and lower minimal SpO2 (OR 0.89, 95%CI 0.81 to 0.98), but not with results of OSA screening tools like BQ score (OR 0.66, 95%CI 0.38 to 1.16), STOP-BANG score (OR 0.73, 95%CI 0.51 to 1.01), NoSAS score (OR 1.01, 95%CI 0.87 to 1.18), or OSA50 score (OR 0.84, 95%CI 0.70 to 1.01). CONCLUSION: Previously undiagnosed OSA was common among hospitalized patients who survived the acute phase of COVID-19. The degree of OSA was associated with the severity of respiratory failure.

Effect of omalizumab on bronchoalveolar lavage matrix metalloproteinases in severe allergic asthma.

INTRODUCTION: Airway inflammation in asthma is accompanied by reconstruction of the bronchial wall extracellular matrix that most likely occurs with a contribution of matrix metalloproteinases (MMPs). Recently we have reported that omalizumab may decrease reticular basement membrane (RBM) thickness together with fibronectin deposits in asthmatic airways, although mechanisms involved are unknown. OBJECTIVE: In the present study, we have investigated the impact of omalizumab on MMPs concentrations in bronchoalveolar lavage fluid (BAL) of asthmatic subjects in relation to airway remodeling changes in histology. PATIENTS AND METHODS: The study group consisted of 13 severe allergic asthmatics treated with omalizumab for at least 12 months. In each subject, clinical and laboratory parameters, bronchoscopy with BAL, and endobronchial biopsy were evaluated before and after the biologic therapy. RBM thickness, fibronectin, and collagen deposits in bronchial mucosa specimens were analyzed in histology. The investigations also included BAL cytology and BAL concentrations of MMP-2, -3, and -9. RESULTS: Omalizumab was related to a decrease in all measured MMPs in BAL (p < 0.001, each), although such declines were not observed in each patient. The depletions were associated with a lower asthma exacerbation rate and better asthma control. Interestingly, patients who showed a decline in at least one MMP (n = 10, 77%) were characterized by a higher decrease in the RBM thickness (-1.61 [-2.02 to -0.6] vs. -0.06 [-0.09 to +3.3], p = 0.03). Likewise, individuals with lower concentrations of MMP-9 after omalizumab (n = 7, 58%) had a greater reduction in the RBM layer as compared to those with steady MMP-9 levels (-1.8 [-2.4 to -1.14] vs. -0.13 [-0.6 to -0.06] µm, p = 0.03). Moreover, the latter group also had unfavorable higher collagen I accumulation after biologic (42 [20 to 55] vs. 0 [-10 to 20]%, respectively, p = 0.03). Higher concentrations of MMPs in BAL at baseline were related to the lower systemic steroid dose and better omalizumab response concerning the decline in RBM thickness. CONCLUSION: Our data suggest that omalizumab therapy is associated with decreased BAL MMPs concentration in the subgroup of asthma patients. The decline was linked with a reduction in the RBM thickness what might play a beneficial role in airway remodeling.

Omalizumab may decrease the thickness of the reticular basement membrane and fibronectin deposit in the bronchial mucosa of severe allergic asthmatics.

Introduction: Immunoglobulin E is an important modulator of the inflammatory reaction in allergic asthma. It also contributes to airway remodeling in the course of the disease. The authors evaluated airway structural changes in severe allergic asthma during the omalizumab therapy. Patients and methods: The study included 13 patients with severe allergic asthma treated with omalizumab for at least one year. In each patient clinical, laboratory, and spirometry parameters were evaluated before and after the treatment. In addition, bronchoscopy with bronchial mucosa biopsy and bronchoalveolar lavage was performed. The basal lamina thickness, inflammatory cell infiltration, fibronectin, as well as type I and III collagen accumulation were assessed in bronchial mucosa specimens, together with the assessment of bronchoalveolar lavage cellularity. Results: The omalizumab therapy led to a decrease in the basal lamina thickness (p = 0.002), and to a reduction in fibronectin (p = 0.02), but not collagen deposits in the bronchial mucosa. The decrease in fibronectin accumulation was associated with an improvement in asthma control and quality of life (p = 0.01, both), and a diminished dose of systemic corticosteroids (p = 0.001). It was also associated with a tendency towards reduction of the eosinophil count in the peripheral blood, bronchoalveolar lavage fluid, and bronchial mucosa specimens. Conclusion: Our study has shown that omalizumab, effective in the treatment of severe allergic asthma, may also decrease unfavorable structural airway changes in allergic asthmatics, at least with respect to the fibronectin deposit and an increased thickness of the basal lamina. However, more extensive observational studies are needed to verify the above hypothesis.

Influence of omalizumab therapy on airway remodeling assessed with high-resolution computed tomography (HRCT) in severe allergic asthma patients.

INTRODUCTION: Airway remodeling is an important factor in persistent obstruction in severe asthma. High resolution computed tomography (HRCT) is an effective method of detecting changes in airway structure. Our aim was to use HRCT to assess changes in airway remodeling in patients with severe allergic asthma who are treated with omalizumab. MATERIAL AND METHODS: In 12 patients with severe allergic asthma, HRCT was performed before and after treatment with omalizumab. In selected bronchi airways, parameters were calculated: bronchial wall area (BA), also corrected for body surface area (BSA); percentage of wall area (WA%); and the ratio of luminal area to total bronchial area (Ai/Ao). Clinical response to treatment was assessed using an asthma control questionnaire (ACQ), asthma quality of life questionnaire (AQLQ), and number of exacerbations per year. Assessment included spirometry and blood eosinophilia. RESULTS: Treatment resulted in significant improvement in ACQ (p = 0.035) and AQLQ (p = 0.001). We observed significant reduction in exacerbations per year (p = 0.002) and reduction of daily systemic steroid dose (p = 0.032). FEV1 and peripheral blood eospinophilia did not change (p = 0.846 and p = 0.221). Airway dimensions (Ai/Ao) of particular bronchi were consistent with the mean of the parameters calculated for all bronchi measured. Although we observed a significant decrease in WA (p = 0.002) and WA/BSA (p = 0.002), WA% and Ai/Ao did not improve (p = 0.39 and p = 0.49). We found no correlations between changes in airways and changes in spirometry or clinical parameters. CONCLUSION: Despite clinical effectiveness of omalizumab, its effect on airway remodeling may be limited.

Autoimmune polyendocrine syndrome type 2 in patient with severe allergic asthma treated with omalizumab.

Asthma therapy with monoclonal antibodies is a promising and effective approach for those with a severe and refractory type of disease. Although such a targeted therapy is considered to be safe, unusual complications may occur. We present a case of a 45 year-old female patient with severe allergic asthma and chronic spontaneous urticaria, who developed autoimmune polyendocrine syndrome type 2 (APS-2) after 26 months of omalizumab administration. The patient was diagnosed with primary adrenal insufficiency (Addison's disease) and Hashimoto's thyroiditis accompanied by autoimmune atrophic gastritis. According to our knowledge this is the first description of APS-2 that developed in conjunction with omalizumab treatment, although we have no evidence that the observed phenomenon indicated a cause-effect relationship to omalizumab.