Here, we studied the IFN-regulated innate immune response against influenza A virus (IAV) infection in the mouse lung and the therapeutic effect of IFN-λ2/3 in acute IAV lung infection. For viral infections, IAV (WS/33, H1N1, PR8 H1N1, H5N1) were inoculated into wild-type mice by intranasal delivery, and IAV mRNA level and viral titer were measured. To compare the antiviral effect of IFNs in vivo in the lung, neutralizing antibodies and recombinant IFNs were used. After intranasal inoculation of IAV into mice, viral infection peaked at 7 days postinfection, and the IAV titer also reached its peak at this time. We found that IFN-β and IFN-λ2/3 were preferentially induced after IAV infection and the IFN-λ2/3–mediated innate immune response was specifically required for the induction of IFN-stimulated genes (ISGs) transcription in the mouse respiratory tract. Neutralization of secreted IFN-λ2/3 aggravated acute IAV lung infection in mice with intact IFN-β induction; consistent with this finding, the transcription of ISGs was significantly reduced. Intranasal administration of IFN-λ2/3 significantly suppressed various strains of IAV infection, including WS/33 (H1N1), PR (H1N1), and H5N1 in the mouse lung, and was accompanied by greater up-regulation of ISGs. Taken together, our data indicate that the IFN-λ2/3–mediated innate immune response is necessary to protect the lungs from IAV infection, and intranasally delivered IFN-λ2/3 has the potential to be a useful therapeutic strategy for treating acute IAV lung infection.

The main mechanism of pathogenesis which causes systemic complications in obstructive sleep apnea (OSA) patients is believed to be intermittent hypoxia-induced intermediary effect and it depends on the burden of oxidative stress during sleep. We aimed to search the predictive markers which reflect the burden of systemic oxidative stress in patients with OSA and whether excessive telomere length shortening is a characteristic feature that can assess oxidative stress levels. We used quantitative PCR to measure telomere length using peripheral blood genomic DNA. Telomere lengths were compared in an age- and body mass index (BMI)-dependent manner in 34 healthy volunteers and 43 OSA subjects. We also performed reactive oxygen species assay to measure the concentration of hydrogen peroxide in the peripheral blood of healthy volunteers and OSA subjects. We found that the serum concentration of hydrogen peroxide was considerably higher in OSA patients, and that this was closely related with the severity of OSA. Significantly shortened telomere length was observed in the circulating leukocytes of the peripheral blood of OSA patients, and telomere length shortening was aggravated more acutely in an age- and BMI-dependent manner. An inverse correlation was observed between the concentration of hydrogen peroxide and the telomere length of OSA patients and excessive telomere length shortening was also linked to severity of OSA. The results provided evidence that telomere length shortening or excessive cellular aging might be distinctive in circulating leukocyte of OSA patients and may be an predictive biomarker for reflect the burden of oxidative stress in the peripheral blood of OSA patients.

Although continuous positive airway pressure (CPAP) is the most effective treatment modality, poor adherence still remains a problem for obstructive sleep apnea (OSA) treatment and there is little evidence regarding how this might be improved. This study aims to analyze the anatomic and clinical factors of OSA subjects who failed to comply with CPAP therapy. The medical records of 47 OSA subjects who received CPAP therapy as a first-line treatment modality were retrospectively reviewed. The medical records were reviewed for demographic and polysomnographic data and anatomic findings of the nasal cavity and oropharynx. 24 patients who adhered to CPAP therapy and 23 patients who were nonadherent were enrolled in the study. There were no statistically significant differences in sleep parameters between CPAP-adherent patients and CPAP nonadherent subjects. Mean body mass index of CPAP nonadherent group was significantly higher than CPAP adherent group. Higher grades of septal deviation and hypertrophic change of the inferior turbinate were observed more in the CPAP nonadherent group. In addition, CPAP nonadherent subjects showed considerably bigger tonsils and higher grade palatal position comparing with the CPAP adherent subjects. Subjective discomfort including inconvenience, mouth dryness, and chest discomfort were the main problems for OSA subjects who did not comply with CPAP therapy. Excessive upper airway blockage in the nasal cavity and oropharynx was predominant in CPAP nonadherent subjects, which might cause the reported subjective discomfort that reduces CPAP compliance. Therefore, resolution of these issues is needed to enhance CPAP compliance for control of OSA.

Importance The lateral pharyngeal wall is recognized as an important site of upper airway collapse during sleep in patients with obstructive sleep apnea (OSA), and expansion sphincter pharyngoplasty (ESP) may have promising clinical utility in patients with OSA and lateral pharyngeal wall collapse. Objectives To evaluate the therapeutic outcomes of ESP in conjunction with other surgical procedures and to investigate indications for ESP in patients with OSA. Design, Setting, and Participants Cohort study of 63 patients with OSA diagnosed with lateral pharyngeal collapse under drug-induced sleep endoscopy who underwent ESP combined with tonsillectomy, uvuloplasty, or nasal surgery at Seoul National University Hospital in Seoul, Korea, between March 1, 2015, and December 1, 2016. Main Outcomes and Measures The primary outcome measure was the change in the apnea-hypopnea index (AHI) after surgery (AHI represents the number of apnea-hypopnea events per hour). Other outcome measures were differences in the surgical response rates, lowest oxygen saturation, subjective visual analog scale scores for snoring and apnea, and Epworth Sleepiness Scale score. Results Fifty of the 63 patients (79%) were male; the mean age was 42.1 (range, 20-54) years, and the mean body mass index (calculated as weight in kilograms divided by height in meters squared) was 27.6 (range, 19.0-32.1). Expansion sphincter pharyngoplasty was performed in patients with OSA with an AHI greater than 15 events per hour, more than 75% retropalatal circumferential narrowing when awake, and narrowed oropharynx due to bulky soft tissue around the lateral pharyngeal wall. In 42 of the 63 patients (67%), ESP was objectively successful in correcting lateral pharyngeal collapse; there was a significant reduction in mean AHI from 35.5 to 17.3 (mean difference, 18.1; 95% CI, 16.3-20.0) and improvement of the lowest mean (SD) oxygen saturation measurement from 78.2% (21.3%) to 86.4% (10.6%) (mean difference, 8.60%; 95% CI, 6.60%-10.60%) 6 months after the operation. The rate of postoperative complications, including pain and bleeding, was minimal after ESP, and a few patients reported an abnormal sensation around the soft palate and swallowing difficulty after ESP. Conclusions and Relevance Expansion sphincter pharyngoplasty appears to be a promising surgical technique to reduce lateral pharyngeal collapse in patients with moderate or severe OSA. Clinical data suggest that both severe palatal circumferential narrowing and bulky lateral pharyngeal tissue are favorable surgical indications for ESP in patients with OSA.