A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants.

While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months. Data from 203 cases (age 0-18 years) were collected from 37 pediatric nephrology centers. Variant pathogenicity was reviewed by a geneticist, and 122 patients with a pathogenic and 19 with a possible pathogenic genotype were included in the analysis. After six months of treatment and at last visit, 27.6% and 22.5% of all patients respectively, demonstrated partial or full response. Achievement of at least partial response at six months of treatment conferred a significant reduction in kidney failure risk at last follow-up compared to no response (hazard ratio [95% confidence interval] 0.25, [0.10-0.62]). Moreover, risk of kidney failure was significantly lower when only those with a follow-up longer than two years were considered (hazard ratio 0.35, [0.14-0.91]). Higher serum albumin level at CNI initiation was the only factor related to increased likelihood of significant remission at six months (odds ratio [95% confidence interval] 1.16, [1.08-1.24]). Thus, our findings justify a treatment trial with a CNI also in children with monogenic SRNS.

Calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene mutations: a systematic review.

BACKGROUND: Calcineurin inhibitor (CNI) use in genetic steroid-resistant nephrotic syndrome (SRNS) is controversial as response rate is reported to be lower than non-genetic disease and no plausible mechanism of action is known. METHODS: We reviewed PubMed for publications on CNI use in hereditary SRNS to determine (1) CNI response rate; (2) impact of response on renal outcome; and (3) clinical and molecular predictors of response. Variant pathogenicity was assessed according to American College of Medical Genetics criteria and patients were assigned to 1 of 4 categories based on estimated genotype contribution to phenotype. Cases with non-existing phenotype-to-genotype contribution were excluded. Subgroup analysis was performed for the possible and confirmed genetic cases. RESULTS: Data of 178 genetic SRNS cases from 22 studies were analyzed; 35% responded (fully or partially) to CNI with minimal change being the commonest biopsy pattern among responders. Full responders had superior kidney survival compared with partial and non-responders (log-rank test χ2 = 10.7; P < 0.01). WT1 variant carriers were most likely to respond to CNI compared with any other mutation [OR 4.7 (2.0-11.3); P < 0.01]. CONCLUSIONS: These findings support the current recommendation for using CNI as first-line treatment for children with SRNS whilst genetic analyses are pending. This would allow assessment of treatment response even in cases later established as genetic ensuring that benefits on kidney function are balanced with treatment toxicity.

Frequency of moderate-to-severe obstructive sleep apnea syndrome among children with snoring and blood pressure in the hypertensive range.

BACKGROUND: It is recommended that children with hypertension and loud snoring should be referred for polysomnography. We aimed to compare the frequency of moderate-to-severe obstructive sleep apnea syndrome (OSAS) among snorers with and without hypertension. Thus, it was hypothesized that systolic or diastolic hypertension among children with snoring is a risk factor for moderate-to-severe OSAS. METHODS: Data of children with snoring and adenotonsillar hypertrophy and/or obesity referred for polysomnography were retrospectively analyzed. Blood pressure (BP) was measured three times in the morning after polysomnography and percentiles were calculated for the average of the second and third measurement. Association of systolic or diastolic hypertension with moderate-to severe OSAS (apnea-hypopnea index-AHI > 5 episodes/h) adjusted for age and obesity was assessed by logistic regression. RESULTS: Data of 646 children with snoring (median age, 6.5 years; 3-14.9 years; 25.7% obese) were analyzed. Prevalence of systolic or diastolic hypertension was 14.1% and 16.1%, respectively and frequency of AHI > 5 episodes/h was 18.3%. Systolic hypertension was a significant predictor of moderate-to-severe OSAS (OR 1.87; 95% CI 1.10 to 3.17; P = 0.02) after adjustment for age and obesity, but diastolic hypertension was not (OR, 0.96; 0.55 to 1.67; P > 0.05). Odds of AHI > 5 episodes/h prior to considering systolic hypertension was 0.25 and after considering its presence, increased to 0.46 (Bayes' theorem), or for every three children with systolic hypertension and snoring tested, one had AHI > 5 episodes/h. CONCLUSIONS: In the context of systolic hypertension and snoring, referral for polysomnography to rule out moderate-to-severe OSAS is a clinically productive practice.

Continuous monitoring of kidney transplant perfusion with near-infrared spectroscopy.

Background: Current reliance on clinical, laboratory and Doppler ultrasound (DUS) parameters for monitoring kidney transplant perfusion in the immediate post-operative period in children risks late recognition of allograft hypoperfusion and vascular complications. Near-infrared spectroscopy (NIRS) is a real-time, non-invasive technique for monitoring tissue oxygenation percutaneously. NIRS monitoring of kidney transplant perfusion has not previously been validated to the gold standard of DUS. We examined whether NIRS tissue oxygenation indices can reliably assess blood flow in established paediatric kidney transplants. Methods: Paediatric kidney transplant recipients ages 1-18 years with stable allograft function were eligible. Participants underwent routine DUS assessment of kidney transplant perfusion, including resistive index (RI) and peak systolic velocity at the upper and lower poles. NIRS data [tissue oxygenation index (TOI%)] were recorded for a minimum of 2 min with NIRS sensors placed on the skin over upper and lower allograft poles. Results: Twenty-nine subjects with a median age of 13.3 (range 4.8-17.8) years and a median transplant vintage of 26.5 months participated. Thirteen (45%) were female and 20 (69%) were living donor kidney recipients. NIRS monitoring was well tolerated by all, with 96-100% valid measurements. Significant negative correlations were observed between NIRS TOI% and DUS RI at both the upper and lower poles (r = -0.4 and -0.6, P = 0.04 and 0.001, respectively). Systolic blood pressure but not estimated glomerular filtration rate also correlated with NIRS TOI% (P = 0.01). Conclusions: NIRS indices correlate well with DUS perfusion and haemodynamic parameters in established paediatric kidney transplant recipients. Further studies are warranted to extend NIRS use for continuous real-time monitoring of early post-transplant perfusion status.

Converting immunosuppression from an oral suspension to a granule formulation of tacrolimus in pediatric renal transplant recipients.

OS of tacrolimus prepared from tacrolimus powder is not licensed for children. A licensed GF for OS allows flexibility for body weight-based dose adjustments. This study aimed at exploring the efficacy of conversion from OS to the GF of tacrolimus in stable pediatric renal transplant recipients. Records of 25 pediatric renal transplant recipients aged under 18 years who were switched from an unlicensed tacrolimus OS to GF were reviewed. At day 0, 1 week, and 4-8 weeks post-conversion, there were no differences regarding daily tacrolimus dose (3.4 ± 3 vs 3.5 ± 2.9 vs 3.5 ± 2.9 mg/day), trough tacrolimus levels (4.5 ± 2.7 vs 4.2 ± 2.7 vs 4.4 ± 3.1 ng/mL), dose-normalized trough tacrolimus levels (1.7 ± 1.1 vs 1.5 ± 1.0 vs 1.7 ± 1.3 ng/mL/mg), PCr (65.6 ± 29.4 vs 67.9 ± 30.4 vs 69.8 ± 27.9 µmol/L), and eGFR (73 ± 24.9 vs 68.7 ± 20.2 vs 65.5 ± 18.2 mL/min/1.73 m2 ) (P > .05). GF dose adjustment was required in 52% of participants. Eighty-eight percent of patients had to return for repeat tacrolimus levels following dose modifications, generating 33 extra visits (≥2 extra visits for 1/3 of subjects). No rejection episodes occurred in the year after conversion. In conclusion, conversion from tacrolimus OS to GF in stable pediatric renal transplant recipients is safe and efficacious. However, close therapeutic drug monitoring in the immediate post-conversion period is necessary.

Infants with viral bronchiolitis demonstrate two distinct patterns of nocturnal oxyhaemoglobin desaturation.

AIM: This study aimed to demonstrate that viral bronchiolitis is associated with intermittent oxygen saturation of haemoglobin (SpO2 ) drops (≥3%) and low basal SpO2 between episodes of haemoglobin desaturation. METHODS: Infants with bronchiolitis underwent pulse oximetry during the first night following hospital admission and a subgroup of them underwent repeat oximetry before hospital discharge. Oximetry was also performed in infants with partial upper airway obstruction (UAO) and without lung disease and in control participants without UAO or lung disease. RESULTS: We enrolled 53 infants: 21 with bronchiolitis, 11 with UAO and 21 healthy controls. Participants with bronchiolitis had lower basal SpO2 (median 93.7% [10th-90th percentiles: 91.1-96.8]) than the subjects with UAO (96.9% [95.3-98.1]; p < 0.01) or the controls (98.7% [96.9-99.3]; p < 0.01). The bronchiolitis group was not different from the UAO group regarding the desaturation index (23.3 episodes/hour [10.3-46.6] and 15.5 episodes/hour [5.4-36.4], respectively; p = 0.08), but differed significantly from the controls (3.1 episodes/hour [0.3-5.5]; p < 0.01). The basal SpO2 and desaturation index improved in 10 subjects with bronchiolitis who had follow-up oximetry before discharge, but these indices remained abnormal when compared to values in the control group. CONCLUSION: Bronchiolitis was characterised by low nocturnal basal SpO2 and intermittent SpO2 drops.

Parental history of adenotonsillectomy is associated with obstructive sleep apnea severity in children with snoring.

OBJECTIVE: To test the hypothesis that history of adenoidectomy and/or tonsillectomy (AT) in at least 1 of the parents during childhood, is a risk factor for moderate-to-severe obstructive sleep apnea (OSA) (apnea-hypopnea index [AHI] >5 episodes/hour) in the offspring with snoring. STUDY DESIGN: Data of children with snoring who were referred for polysomnography over 12 years by primary care physicians were reviewed. RESULTS: Data of 798 children without history of prior AT, neuromuscular, or genetic disorders or craniofacial abnormalities were analyzed. Of these children, 69.3% had tonsillar hypertrophy, 25.8% were obese, 26.8% had at least 1 parent with history of AT, and 22.1% had AHI >5 episodes/hour. Parental history of AT was significantly associated with moderate-to-severe OSA (logit model including sex, tonsillar hypertrophy, obesity, and physician-diagnosed wheezing; OR [95% CI], 1.70 [1.18-2.46]; P < .01). When significant variables from the logit model (tonsillar hypertrophy, obesity, parental history of AT) were considered independently or in combination, tonsillar hypertrophy combined with history of AT in at least 1 of the parents had high specificity (84.4%) and the highest positive likelihood ratio (1.78) for identifying children with AHI >5 episodes/hour. CONCLUSIONS: Among children with snoring who are referred for polysomnography by primary care physicians, those with tonsillar hypertrophy and parental history of AT have increased risk of moderate-to-severe OSA and represent 1 of the subgroups that should be prioritized for a sleep study in settings with limited resources.

Nocturnal enuresis is associated with moderate-to-severe obstructive sleep apnea in children with snoring.

BACKGROUND: Conflicting data suggest that prevalence of monosymptomatic primary nocturnal enuresis (NE) increases with increasing severity of obstructive sleep apnea (OSA) in childhood and especially in girls. We hypothesized that NE is associated with increased risk of moderate-to-severe OSA (obstructive apnea-hypopnea index (AHI) >5 episodes/hour) among children with snoring. METHODS: Data of children (≥5 y old) with snoring who were referred for polysomnography over 12 y were reviewed. RESULTS: Data of 525 children with mean age (±SD) 7.5 (± 2.2) y and median obstructive AHI (10th-90th percentiles) 1.9 (0.4-7.3) episodes/hour were analyzed. Three hundred and fifty-five children (67.6%) had NE and 87 (16.6%) had moderate-to-severe OSA. There was no interaction between NE and gender regarding the association with moderate-to-severe OSA (P > 0.05). NE was associated significantly with presence of moderate-to-severe OSA after adjustment for tonsillar hypertrophy, obesity, gender, and age (adjusted odds ratio = 1.92 (1.08-3.43); P = 0.03). Presence of NE had high sensitivity (78.2%) and low positive predictive value (19.2%) for detecting moderate-to-severe OSA and low specificity (34.5%) and high negative predictive value (88.8%) for ruling it out. CONCLUSION: Children with snoring and without NE referred for polysomnography are less likely to have moderate-to-severe OSA compared to those with NE.

Low-grade albuminuria in children with obstructive sleep apnea.

Small urinary protein loss (low-grade albuminuria or microalbuminuria) may reflect altered permeability of the glomerular filtration barrier. In the present study, it was hypothesized that children with obstructive sleep apnea have an increased risk of microalbuminuria compared with control subjects without sleep-disordered breathing. Albumin-to-creatinine ratio was measured in morning spot urine specimens collected from consecutive children with or without snoring who were referred for polysomnography. Three groups were studied: (i) control subjects (no snoring, apnea-hypopnea index < 1 episode h(-1) ; n = 31); (ii) mild obstructive sleep apnea (snoring, apnea-hypopnea index = 1-5 episodes h(-1) ; n = 71); and (iii) moderate-to-severe obstructive sleep apnea (snoring, apnea-hypopnea index > 5 episodes∙h(-1) ; n = 27). Indications for polysomnography in control subjects included nightmares, somnambulism and morning headaches. An albumin-to-creatinine ratio > median value in the control group (1.85 mg of albumin per g of creatinine) was defined as elevated. Logistic regression analysis revealed that children with moderate-to-severe obstructive sleep apnea, but not those with mild obstructive sleep apnea, had increased risk of elevated albumin-to-creatinine ratio relative to controls (reference) after adjustment for age, gender and presence of obesity: odds ratio 3.8 (95% confidence interval 1.1-12.6); P = 0.04 and 1.5 (0.6-3.7); P > 0.05, respectively. Oxygen desaturation of hemoglobin and respiratory arousal indices were significant predictors of albumin-to-creatinine ratio (r = 0.31, P = 0.01; and r = 0.43, P < 0.01, respectively). In conclusion, children with moderate-to-severe obstructive sleep apnea are at significantly higher risk of increased low-grade excretion of albumin in the morning urine as compared with control subjects without obstructive sleep apnea. These findings may reflect altered permeability of the glomerular filtration barrier related to nocturnal hypoxemia and sympathetic activation which are induced by obstructive sleep apnea.

Effect of Leflunomide on Treatment of Pediatric Renal Transplant Recipients With BK Virus Infection.

OBJECTIVES: Infection with the BK virus is a significant complication after renal transplant and can progress to BK virus nephropathy and graft dysfunction. There is no consensus on the management of BK virus infection in pediatric renal transplant recipients. The most common therapeutic option is immunosuppression reduction, which can increase rejection risk. We aimed to examine the effect of leflunomide, an agent with antiviral and immunosuppressive actions, in a case series of pediatric renal transplant recipients with BK virus infection. MATERIALS AND METHODS: Routine screening with blood BK virus DNA polymerase chain reaction was performed regularly in all of our renal transplant patients. When BK virus was detected, we reduced tacrolimus levels, discontinued mycophenolate mofetil, and started active treatment with leflunomide. Treatment with leflunomide was continued until BK virus was undetectable by polymerase chain reaction in at least 2 blood samples 2 weeks apart. RESULTS: All pediatric patients developed BK virus infection in a mean period of 3.9 months after transplant. Graft dysfunction was evident in all patients with 20% to 100% elevation of creatinine from baseline. Afterleflunomide initiation, all patients had undetectable levels of BK virus by plasma polymerase chain reaction in at least 2 different samples within a mean period of 3.4 months, and renal function had normalized back to the baseline. None of our patients had evidence of hepatotoxicity or anemia on regular monitoring, with no other adverse events. Renal function remained stable in the follow-up period with no reoccurrence of BK viremia up to the date of this writing. CONCLUSIONS: Treatment with leflunomide resulted in rapid BK virus clearance and preservation of renal function with no adverse effects.

Oxidative stress and inflammatory markers in the exhaled breath condensate of children with OSA.

INTRODUCTION: Obstructive sleep apnea (OSA) in children has been associated with systemic inflammation and oxidative stress. Limited evidence indicates that pediatric OSA is associated with oxidative stress and inflammation in the airway. OBJECTIVE: The objective of this study is to assess the hypothesis that levels of oxidative stress and inflammatory markers in the exhaled breath condensate (EBC) of children with OSA are higher than those of control subjects. METHODS: Participants were children with OSA and control subjects who underwent overnight polysomnography. Morning levels of hydrogen peroxide (H(2)O(2)) and sum of nitrite and nitrate (NO(x)) in EBC of participants were measured. RESULTS: Twelve subjects with moderate-to-severe OSA (mean age ± standard deviation: 6.3 ± 1.7 years; apnea-hypopnea index--AHI, 13.6 ± 10.1 episodes/h), 22 subjects with mild OSA (6.7 ± 2.1 years; AHI, 2.8 ± 1 episodes/h) and 16 control participants (7.7 ± 2.4 years; AHI, 0.6 ± 0.3 episodes/h) were recruited. Children with moderate-to severe OSA had higher log-transformed H(2)O(2) concentrations in EBC compared to subjects with mild OSA, or to control participants: 0.4 ± 1.1 versus -0.9 ± 1.3 (p = 0.015), or versus -1.2 ± 1.2 (p = 0.003), respectively. AHI and % sleep time with oxygen saturation of hemoglobin <95% were significant predictors of log-transformed H(2)O(2) after adjustment by age and body mass index z score (p < 0.05). No significant differences were demonstrated between the three study groups in terms of EBC NO(x) levels. CONCLUSIONS: Children with moderate-to-severe OSA have increased H(2)O(2) levels in morning EBC, an indirect index of altered redox status in the respiratory tract.

Serum leukotriene B4 levels, tonsillar hypertrophy and sleep-disordered breathing in childhood.

OBJECTIVES: In children with snoring, increased production of leukotriene B4 (LTB4) may promote tonsillar hypertrophy and sleep-disordered breathing (SDB) or conversely SDB may enhance LTB4 synthesis. We explored whether: i) high LTB4 serum levels predict tonsillar hypertrophy; and ii) SDB severity correlates with LTB4 serum concentration. METHODS: Normal-weight children with SDB or controls underwent polysomnography and measurement of LTB4 serum concentration. Tonsillar hypertrophy was the main outcome measure and high LTB4 serum level (>75 t h percentile value in controls) was the primary explanatory variable. Odds ratio (OR) and the corresponding 95% confidence intervals (CI) for tonsillar hypertrophy in children with versus without high LTB4 level were calculated. The control subgroup and subgroups of subjects with increasing SDB severity were compared regarding LTB4 concentration by Kruskal-Wallis test. Spearman's correlation co-efficient was applied to assess the association of LTB4 concentration with SDB severity. RESULTS: A total of 104 children with SDB and mean obstructive apnea-hypopnea index-AHI of 4.8 ±â€¯5.3 episodes/h (primary snoring: n = 19; mild SDB: n = 49; moderate/severe SDB: n = 36) and 13 controls (no snoring; AHI: 0.4 ±â€¯0.2 episodes/h) were recruited. The four study subgroups were similar regarding LTB4 serum concentration (P = 0.64). High LTB4 (>170.3 pg/mL) was a significant predictor of tonsillar hypertrophy after adjustment for age and gender (OR 3.0 [1.2-7.2]; P = 0.01). There was no association between AHI or desaturation index and LTB4 serum concentration (r = -0.08; P = 0.37 and r = -0.1; P = 0.30, respectively). CONCLUSION: No association was identified between SDB severity and LTB4 levels, but high LTB4 concentration predicted tonsillar hypertrophy.

Family history of adenotonsillectomy as a risk factor for tonsillar hypertrophy and snoring in childhood.

OBJECTIVE: Accumulating evidence supports a role for familial predisposition in the pathogenesis of OSA. In this study, it was hypothesized that parental history of adenoidectomy and/or tonsillectomy (AT), which is the standard treatment for pediatric OSA is a risk factor for tonsillar hypertrophy and habitual snoring (>3 nights/week) in the offspring. METHODS: Children were recruited from the emergency department and the pediatric pulmonology clinic. Paternal or maternal history of AT (explanatory variables) and habitual snoring (outcome) were recorded and presence of tonsillar hypertrophy (outcome) was assessed. RESULTS: Two hundred ninety-two children (2-14 y.o.) were recruited; 37 (12.7%) of them had paternal history of AT, 39 (13.4%) maternal history of AT, 60 (20.5%) tonsillar hypertrophy, and 48 (16.4%) habitual snoring. Maternal and paternal history of AT were significantly associated with the presence of tonsillar hypertrophy even after adjustment for age, gender, obesity, passive smoking, and physician-diagnosed wheezing requiring treatment with inhaled medications over the past year [odds ratios (95% confidence interval): 3.52 (1.54-8.06); P < 0.01 and 4.70 (2.13-10.36); P < 0.01, respectively]. Only maternal history of AT predicted history of snoring [4.12 (1.86-9.12); P < 0.01]. When entered in the same multivariate logistic regression analysis model, tonsillar hypertrophy was a stronger predictor of habitual snoring than maternal history of AT [4.00 (1.97-8.14) vs. 2.73 (1.20-6.20)]. CONCLUSIONS: Children with parental history of AT have more frequently tonsillar hypertrophy than those without such history. Tonsillar hypertrophy mediates at least in part the association between maternal history of AT and habitual snoring in childhood.

Viral croup: diagnosis and a treatment algorithm.

Viral croup is a frequent disease in early childhood. Although it is usually self-limited, it may occasionally become life-threatening. Mild croup is characterized by the presence of stridor without intercostal retractions, whereas moderate-to-severe croup is accompanied by increased work of breathing. A single dose of orally administered dexamethasone (0.15-0.6 mg/kg) is the mainstay of treatment with addition of nebulized epinephrine only in cases of moderate-to-severe croup. Nebulized budesonide (2 mg) can be given alternatively to children who do not tolerate oral dexamethasone. Exposure to cold air or administration of cool mist are treatment interventions for viral croup that are not supported by published evidence, but breathing heliox can potentially reduce the work of breathing related to upper airway obstruction. In summary, corticosteroids may decrease the intensity of viral croup symptoms irrespective to their severity on presentation to the emergency department.

Obstructive sleep apnea, excessive daytime sleepiness, and morning plasma TNF-α levels in Greek children.

BACKGROUND: Obstructive sleep apnea (OSA) has been associated with increased frequency of excessive daytime sleepiness (EDS). Increased plasma TNF-α levels may mediate this association in adults, but conflicting results have been reported in children. We hypothesized that: (i) the higher the OSA severity in childhood, the higher the frequency of EDS and morning plasma TNF-α levels; and (ii) high TNF-α levels predict presence of EDS. METHODS: Children without and with snoring underwent polysomnography. EDS was determined by parental response to specific questions, and plasma TNF-α levels were measured. RESULTS: Children with moderate-to-severe OSA (n = 24; 5.7 ± 2 years; apnea-hypopnea index [AHI] 11.5 ± 5.1/h), but not participants with mild OSA (n = 22; 6 ± 2.5 years; AHI 2.1 ± 1/h) were at significantly higher risk for EDS than controls (n = 22; 6.8 ± 2.1 years; AHI 0.5 ± 0.3/h) (OR [95% CI] adjusted for age, gender, and obesity: 9.2 [1.7-50.2] and 3.8 [0.7-21.8], respectively). The 3 groups did not differ regarding TNF-α concentration (0.63 ± 0.2 vs 0.65 ± 0.18 vs 0.63 ± 0.17 pg/mL; P > 0.05). TNF-α levels were associated significantly with body mass index z-score (P < 0.05) and not with polysomnography indices (P > 0.05). Subjects with high TNF-α levels (> 0.57 pg/mL) were not at higher risk for EDS than participants with low levels (OR [95% CI] adjusted for age, gender, and obesity: 1.7 [0.5-5.7]). CONCLUSIONS: Increasing severity of OSA is associated with increasing frequency of EDS, but not with elevated plasma TNF-α concentration. High TNF-α levels cannot be used as predictor for the presence of EDS in children with sleep apnea.

Low morning serum cortisol levels in children with tonsillar hypertrophy and moderate-to-severe OSA.

BACKGROUND: Hypertrophic tonsillar tissue in children with obstructive sleep apnea (OSA) has enhanced expression of glucocorticoid receptors, which may reflect low endogenous cortisol levels. We have evaluated the effect of the interaction between tonsillar hypertrophy and OSA severity on morning serum cortisol levels. METHODS: Children with and without snoring underwent polysomnography, tonsillar size grading, and measurement of morning serum cortisol. RESULTS: Seventy children (2-13 years old) were recruited: 30 with moderate-to-severe OSA (apnea-hypopnea index [AHI] > 5 episodes/h), 26 with mild OSA (AHI > 1 and ≤ 5), and 14 controls (no snoring; AHI ≤ 1). Tonsillar hypertrophy was present in 56.7%, 53.8%, and 42.9% of participants in each group, respectively. Application of a general linear model demonstrated a significant effect of the interaction between severity of OSA and tonsillar hypertrophy on cortisol levels (P = 0.04), after adjustment for obesity, gender, and age. Among children with tonsillar hypertrophy, subjects with moderate-to-severe OSA (n = 17; AHI 14.7 ± 10.6), mild OSA (n = 14; AHI 2.3 ± 1.2), and control participants (n = 6; AHI 0.7 ± 0.2) were significantly different regarding cortisol levels (P = 0.02). Subjects with moderate-to-severe OSA had lower cortisol (16.9 ± 8.7 mcg/dL) than those with mild OSA (23.3 ± 4.2; P = 0.01) and those without OSA (controls) (23.6 ± 5.3 mcg/dL; P = 0.04). In contrast, children with normal-size tonsils and moderate-to-severe OSA, mild OSA, and controls did not differ in cortisol levels. CONCLUSIONS: Children with moderate-to-severe obstructive sleep apnea and the phenotype of hypertrophic tonsils have reduced morning serum cortisol levels and potentially decreased glucocorticoid inhibitory effects on tonsillar growth.

Interactions of obstructive sleep-disordered breathing with recurrent wheezing or asthma and their effects on sleep quality.

Snoring is the most characteristic symptom of obstructive sleep-disordered breathing (SDB) and recurrent wheezing is the most common clinical manifestation of asthma. The purpose of the present review is to outline the impact of SDB and recurrent wheezing/asthma on sleep quality and to summarize the epidemiologic and pathophysiologic evidence supporting an association between the two disorders. Enlarged tonsils and adenoid or obesity predispose to obstructive sleep apneas and hypopneas which are accompanied by arousals, restless sleep, and frequently daytime sleepiness, inattention, hyperactivity, and academic difficulties. Subjects with history of wheezing are also at risk for sleep disturbance and daytime cognitive dysfunction. Asthmatic children have more frequent snoring, apneas, and hypopneas during sleep than non-asthmatic subjects and tonsillar hypertrophy mediates at least in part this epidemiologic association. In addition, preliminary evidence indicates that treatment of sleep apnea with adenotonsillectomy results in improved control of coexisting asthma. Elevated concentrations of leukotrienes and oxidative stress markers have been detected in the exhaled breath condensate of children with asthma and probably contribute to bronchoconstriction. Moreover, sleep apneic children have increased expression of leukotrienes and leukotriene receptors in adenotonsillar tissue. Viral respiratory infections may induce inflammation and oxidative stress in the asthmatic airway enhancing not only bronchospasm, but also biosynthesis of leukotrienes within pharyngeal lymphoid tissues, which promote adenotonsillar enlargement and sleep apnea. In conclusion, taking under consideration the epidemiologic association between obstructive SDB and asthma, when one of the two disorders is diagnosed, the possibility of the other disease being present should be entertained. Pediatr. Pulmonol. 2011; 46:1047-1054. © 2011 Wiley Periodicals, Inc.