Cysteinyl Leukotriene Receptors Are Expressed by Tonsillar T Cells of Children With Obstructive Sleep Apnea

Kaditis, Athanasios G.; Ιωάννου, Μαρία; Chaidas, Konstantinos; Alexopoulos, Emmanouel Ι.; Apostolidou, Maria; Apostolidis, Theoharis; Koukoulis, George N.; Gourgoulianis, Konstantinos

doi:10.1378/chest.07-2746

Cited by 65 publications

(37 citation statements)

References 36 publications

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“…Similarly, FLU has been found to have increased potency compared with BUD in inhibiting human T-cell migration and proliferation, and inhibiting CD4+ T-cell cytokine release, and in stimulating inflammatory cell apoptosis [30]. Considering the increased abundance of T-cells, particularly CD4+ T-cells, in the tonsillar tissues of children with OSA [31], and the important roles that these cell populations may have in local regulation of immune responses and proliferation [32][33][34], the use of CS as therapeutic tools seems a logical approach in an attempt to reduce T-cell proliferation and promote apoptosis, while reducing pro-inflammatory cytokine production [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Corticosteroids suppressin vitrotonsillar proliferation in children with obstructive sleep apnoea

Kheirandish‐Gozal¹,

Serpero²,

Dayyat³

et al. 2008

Eur Respir J

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Intranasal corticosteroids (CS) are potentially useful interventions for children with obstructive sleep apnoea (OSA), and may reduce lymphadenoid tissue size in the upper airway. The present authors hypothesised that CS would reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil/adenoid mixed-cell culture system. Dissociated tonsils or adenoids harvested intra-operatively from children with polysomnographically diagnosed OSA were cultured in control medium (CO) or after stimulation with lipopolysaccharide and concanavalin A (STIM), and incubated with dexamethasone (DEX; 10 ; n554). DEX, FLU and BUD reduced cellular proliferation rates, and exhibited dose-dependent effects, with the potency being FLU.BUD.DEX (n525 per group). Conversely, CS increased cellular apoptosis (n520 per group). Furthermore, TNF-a, IL-8 and IL-6 concentrations in the supernatant were increased by STIM, and markedly reduced by all CS (n548 per group).Whole tissue cell cultures of adenoids and tonsils provide a useful approach for in vitro assessment of therapeutic efficacy of corticosteroids in the management of lymphadenoid hypertrophy that underlies obstructive sleep apnoea in children.

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Section: Discussionmentioning

confidence: 99%

Corticosteroids suppressin vitrotonsillar proliferation in children with obstructive sleep apnoea

Kheirandish‐Gozal¹,

Serpero²,

Dayyat³

et al. 2008

Eur Respir J

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“…Indeed, intranasal corticosteroids have shown favorable outcomes in children with OSA, and their use for periods of 4 to 6 weeks has been associated with improvements in the respiratory disturbance during sleep and partial involution of adenoidal hypertrophy. 10 -14 Furthermore, increased concentrations of leukotrienes (LTs) in Original Research SLEEP MEDICINE tonsils and upper airway condensate in children with OSA along with a relatively high abundance of LT receptors in these tissues suggested that LT pathways may contribute to the proliferative status of adenotonsillar tissues, 15,16 and in fact, improvements in sleep disturbances occurred after treatment in an open-label trial of children with mild OSA. 17 We recently developed 18 a novel method allowing for in vitro cell culture of tonsils and adenoids derived from children undergoing tonsillectomy and adenoidectomy (T&A).…”

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confidence: 99%

Leukotriene Pathways and In Vitro Adenotonsillar Cell Proliferation in Children With Obstructive Sleep Apnea

Dayyat

Serpero

Kheirandish‐Gozal

et al. 2009

Chest

108

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Introduction:The abundant expression of leukotrienes (LTs) and their receptors in adenotonsillar tissues of children with obstructive sleep apnea (OSA) suggest that LT antagonists could be useful in treating OSA. Methods: The effects of LTD4 and of LT receptor antagonists zileuton, montelukast, and BAY u9773 were examined on mixed cell cultures prepared from dissociated tonsils or adenoids harvested intraoperatively from children with polysomnographically diagnosed OSA. Proliferation was assessed by 3 [H]-thymidine incorporation, and inflammatory cytokine production (tumor necrosis factor [TNF]-␣, interleukin [IL]-6, IL-8, IL-10, and IL-12) was assessed in supernatants using enzyme-linked immunosorbent assay.Results: LTD4 elicited dose-dependent increases in adenotonsillar cell proliferation (p < 0.001; n ‫؍‬ 12). All LT antagonists exhibited dose-dependent reductions in adenotonsillar cellular proliferation rates, with montelukast more than BAY u9773 more than zileuton (n ‫؍‬ 14/group; p < 0.001). However, BAY u9773 showed partial agonist effects and increased cellular proliferation at higher concentrations (10 ؊4 mmol/L; p < 0.01; n ‫؍‬ 12). LTD4 effects were partially blocked by montelukast and BAY u9773 but not by zileuton. All three antagonists reduced TNF-␣, IL-6, and IL-12 concentrations, with selective changes in IL-8 and no effects on IL-10 levels. Conclusions: LT pathways mediate intrinsic proliferative and inflammatory signaling pathways in adenotonsillar tissues from children with OSA, and targeted pharmacologic disruption of these pathways may provide nonsurgical alternatives for prevention and treatment of this disease.

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“…2 Moreover, the level of leukotrienes and their receptors are increased in the tonsils and adenoids of children with OSA. 3 Montelukast, an oral leukotriene receptor antagonist, has been approved for preventive treatment of inflammation associated with asthma and allergic rhinitis in children older than 1 y. Oral montelukast has been used in children with mild to moderate OSA.…”

Section: Discussionmentioning

confidence: 99%

A Four-Year-Old Boy with Unusually Severe Obstructive Sleep Apnea

Zhou

Yang

et al. 2017

Journal of Clinical Sleep Medicine

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frequent and very severe reductions in blood oxygen saturation (SpO 2 , lowest at 55%). Persistent, large-range variations in heart rate (70-140 beats/min) were associated with frequent OSA events and occurred throughout the night. The radiograph showed nasopharyngeal stenosis with tonsil and adenoid hypertrophy (adenoidal nasopharyngeal ratio (A/N): 0.92; normal range < 0.5-0.6).The patient's parents did not want to consider surgery and preferred medication as a first treatment. Therefore, montelukast (oral, 5 mg/day) was prescribed. After taking montelukast for 2 mo, the patient's frequency and severity of snoring was reduced. Repeat polysomnogram showed a surprising reduction in the AHI to 2.4 events/h during a total sleep time of 8.19 h (supine position 34%, REM 19.4%). Overnight measurements of SpO 2 and heart rate stabilized to nearly normal levels ( Figure 1B). The nasopharyngeal airway also appeared wider in the radiograph (A/N: reduced from 0.92 to 0.80).A 4-y-old boy presented with frequent snoring and mouth breathing, but no other symptoms often seen in children with obstructive sleep apnea (OSA) (e.g., observed episodes of apnea, daytime sleepiness, enuresis, and hyperactivity). His mother stated that the frequency and severity of his snoring varied from time to time. He did not frequently have colds, estimated at once or twice a year. He had normal physical and mental development (height 110 cm, body weight 19 kg, body mass index 15.7 kg/m 2 ). He appeared to have a mild adenoid face (a slightly short upper lip with mandibular hypoplasia) and obvious tonsillar hypertrophy (grade 3+ tonsils with < 75% of space between pillars) and a stage II Friedman classification.The patient underwent overnight polysomnography, and a radiograph of the lateral neck was obtained. Surprisingly, we found that the patient had unusually severe OSA based on the apnea-hypopnea index (AHI), which was as high at 102.5 events/h. During a recorded total sleep time of 7.75 h (supine position 64%, rapid eye movement (REM) sleep 25.1%), he had 713 obstructive apnea events (longest at 53 sec), 73 hypopnea events (longest at 55 sec) and 8 mixed apnea events (longest at 31 sec) but no central sleep apnea events. As demonstrated in Figure 1A, the patient experienced SLEEP MEDICINE PEARLS

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Cysteinyl Leukotriene Receptors Are Expressed by Tonsillar T Cells of Children With Obstructive Sleep Apnea

Cited by 65 publications

References 36 publications

Corticosteroids suppressin vitrotonsillar proliferation in children with obstructive sleep apnoea

Corticosteroids suppressin vitrotonsillar proliferation in children with obstructive sleep apnoea

Leukotriene Pathways and In Vitro Adenotonsillar Cell Proliferation in Children With Obstructive Sleep Apnea

A Four-Year-Old Boy with Unusually Severe Obstructive Sleep Apnea

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