Obstructive sleep apnea in obese adolescents referred for bariatric surgery: association with metabolic and cardiovascular variables.

BACKGROUND: obstructive sleep apnea syndrome (OSA) is a well-described disease entity in adults, with a higher prevalence in severely obese individuals, while at the same time associated with several comorbidities independently of BMI. Literature regarding OSA in severely obese adolescents is qualitatively and quantitatively limited, possibly resulting in suboptimal diagnosis and treatment. METHODS: polysomnographic, demographic, anthropometric, and comorbidity-related data were prospectively collected in 56 adolescents with morbid obesity refractory to conservative treatment who presented for surgical therapy. Differences between adolescents with no/mild (apnea-hypopnea index (AHI) 0-4.9) and moderate/severe OSA (AHI ≥ 5.0) were evaluated using independent-samples t, chi-square or Fisher's exact tests. Multivariable linear regression analysis was performed to evaluate the association of several variables with AHI, corrected for BMI z-score. RESULTS: of the 53 included subjects, 48 (90.6%) showed some degree of sleep disordered breathing and 20 (37.7%) had moderate/severe OSA. Patients with moderate/severe OSA had on average a higher neck circumference (42.4 versus 40.1 cm, p = 0.008), higher BMI z-score (3.7 versus 3.4, p = 0.003), higher plasma triglyceride level (2.2 versus 1.5 mmol/L, p = 0.012), and lower IGF (29.6 versus 40.2 mmol/L, p = 0.010) than those with no/mild OSA. BMI z-score and plasma triglyceride levels were independently related to AHI. CONCLUSIONS: OSA is highly prevalent amongst morbidly obese adolescents and is strongly associated with BMI z-score. Elevated plasma triglyceride levels are associated with AHI, independent of BMI z-score.

Risk factors for lung disease progression in children with cystic fibrosis.

To identify potential risk factors for lung disease progression in children with cystic fibrosis (CF), we studied the longitudinal data of all children with CF (aged ≥5 years) registered in the Dutch CF Registry (2009-2014).Lung disease progression was expressed as a decline in lung function (forced expiratory volume in 1 s (FEV1) % pred) and pulmonary exacerbation rate. Potential risk factors at baseline included sex, age, best FEV1 % pred, best forced vital capacity % pred, genotype, body mass index z-score, pancreatic insufficiency, medication use (proton pump inhibitors (PPIs), prophylactic antibiotics and inhaled corticosteroids), CF-related diabetes, allergic bronchopulmonary aspergillosis and colonisation with Pseudomonas aeruginosaThe data of 545 children were analysed. PPI use was associated with both annual decline of FEV1 % pred (p=0.017) and future pulmonary exacerbation rate (p=0.006). Moreover, lower FEV1 % pred at baseline (p=0.007), prophylactic inhaled antibiotic use (p=0.006) and pulmonary exacerbations in the baseline year (p=0.002) were related to pulmonary exacerbations in subsequent years.In a cohort of Dutch children with CF followed for 5 years, we were able to identify several risk factors for future exacerbations. In particular, the association between PPI use and lung disease progression definitely requires further investigation.

Introducing a core curriculum for respiratory sleep practitioners.

The background and purpose of the HERMES (Harmonising Education in Respiratory Medicine for European Specialists) initiative has been discussed at length in previous articles [1-3]. This article aims to provide more detailed and specific insight into the process and methodology of the Sleep HERMES Task Force in developing a core curriculum in respiratory sleep medicine.

Baroreflex activation therapy lowers arterial pressure without apparent stimulation of the carotid bodies.

Carotid baroreflex activation therapy produces a sustained fall in blood pressure in patients with resistant hypertension. Because the activation electrodes are implanted at the level of the carotid sinus, it is conceivable that the nearby located carotid body chemoreceptors are stimulated as well. Physiological stimulation of the carotid chemoreceptors not only stimulates respiration but also increases sympathetic activity, which may counteract the effects of baroreflex activation. The aim of this exploratory study is to investigate whether there is concomitant carotid chemoreflex activation during baroreflex activation therapy. Fifteen participants with the Rheos system were included in this single-center study. At arrival at the clinic, the device was switched off for 2 hours while patients were at rest. Subsequently, the device was switched on at 6 electric settings of high and low frequencies and amplitudes. Respiration and blood pressure measurements were performed during all device activation settings. Multilevel statistical models were adjusted for age, sex, body mass index, antihypertensive therapeutic index, sleep apnea, coronary artery disease, systolic blood pressure, and heart rate. There was no change in end-tidal carbon dioxide, partial pressure of carbon dioxide, breath duration, and breathing frequency during any of the electric settings with the device. Nevertheless, mean arterial pressure showed a highly significant decrease during electric activation (P<0.001). Carotid baroreflex activation therapy using the Rheos system did not stimulate respiration at several electric device activation energies, which suggests that there is no appreciable coactivation of carotid body chemoreceptors during device therapy.

Case Report: Bilateral diaphragmatic dysfunction due to Borrelia Burgdorferi.

SUMMARY: In this case report we describe a rare case of bilateral diaphragmatic dysfunction due to Lyme disease. CASE REPORT: A 62-years-old male presented to the hospital because of flu-like symptoms. During initial evaluation a bilateral diaphragmatic weakness with orthopnea and nocturnal hypoventilation was observed, without a known aetiology. Bilateral diaphragmatic paralysis was confirmed by fluoroscopy with a positive sniff test. The patient was referred to our centre for chronic non-invasive nocturnal ventilation (cNPPV). Subsequent investigations revealed evidence of anti- Borrelia seroactivity in EIA-IgG and IgG-blot, suggesting a recent infection with Lyme disease, and resulted in a 4-week treatment with oral doxycycline. The symptoms of nocturnal hypoventilation were successfully improved with cNPPV. However, our patient still shows impaired diaphragmatic function but he is no longer fully dependent on nocturnal ventilatory support.     CONCLUSION: Lyme disease should be considered in the differential diagnosis of diaphragmatic dysfunction. It is a tick-borne illness caused by one of the three pathogenic species of the spirochete Borrelia burgdorferi, present in Europe. A delay in recognizing the symptoms can negatively affect the success of treatment. Non-invasive mechanical ventilation (NIV) is considered a treatment option for patients with diaphragmatic paralysis.

Respiratory impedance in healthy subjects: baseline values and bronchodilator response.

Because of the minimal demand for cooperation by the subject, the forced oscillation technique is increasingly employed in routine lung function testing. However, comprehensive and device-independent values of respiratory impedance at baseline and after bronchodilation have not been established for healthy adults. The aim of this multicentre study was to collect impedance data from 4 to 26 Hz in healthy Caucasian subjects between 18 and 80 years of age. Five different devices were employed to assess baseline values and the bronchodilator response. Altogether, 368 subjects were examined. Despite adjustment for anthropometry, the impedance spectra differed in frequency dependence between the centres, and hence could not be pooled. However, resistance at all frequencies except 20 and 25 Hz, and the low-frequency (≤14 Hz) values of reactance did not exhibit a centre dependence. The regression equations for resistance reflected a greater height dependence in males and a greater weight dependence in both males and females than those published previously. Bronchodilation resulted in a statistically significant decrease (11%) in resistance and a 95th percentile equal to a 32% decrease in resistance at low frequency. We conclude that rigorous calibration procedures should be developed to ensure data compatibility. Furthermore, new reference equations based on different setups are recommended to replace those established with a single device.

Is there an added value of cardiopulmonary exercise testing in sarcoidosis patients?

BACKGROUND: Cardiopulmonary exercise testing (CPET) with blood gas analysis may be helpful when there is a discrepancy between clinical findings and physiologic tests at rest. The aim of this study was to examine the added value of CPET compared to the measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) in detecting impaired pulmonary gas exchange in sarcoidosis patients. METHODS: The clinical records of 160 (age = 41.3 ± 10.0 years; number of females = 63) sarcoidosis patients referred to the former MUMC ild care center were retrospectively reviewed. Patients performed a symptom-limited incremental exercise test with blood gas analysis on a bicycle ergometer. DLCO was measured by the single-breath method. RESULTS: DLCO (mean = 83.2 ± 18.0 %) below 80 % of predicted was demonstrated by 38 % of the sarcoidosis patients in our sample. Of the patients with normal DLCO (n = 99, 61.9 %), the P(A-a)O(2) at maximal exercise [P(A-a)O(2)max] was moderately increased (>2.5 kPa) in 69.7 % and excessively increased (>4.7 kPa) in 18.2 %. Pulmonary gas exchange impairment (PGEI) was more obvious in patients with lower DLCO values. A DLCO value below 60 % of predicted indicated substantial gas exchange impairment. PaO(2) at rest, DLCO, and FVC as a percentage of predicted and radiographic staging predicted 40 % of the PGEI at maximal exercise. CONCLUSION: A substantial number of the symptomatic sarcoidosis patients with normal DLCO appeared to have PGEI at maximal exercise, suggesting that normal DLCO at rest is an inappropriate predictor of abnormal pulmonary gas exchange during exercise. CPET appeared to offer added value in detecting impaired gas exchange during exercise in sarcoidosis patients with unexplained disabling symptoms.

Elevated inflammatory markers at preschool age precede persistent wheezing at school age.

BACKGROUND: Wheeze is a heterogeneous symptom in preschool children. At preschool age it is hard to predict whether symptoms will pass or persist and develop into asthma. Our objective is to prospectively study whether inflammatory markers in exhaled breath condensate (EBC) and pre- and post-bronchodilator interrupter resistance (Rint) assessed at preschool age, are associated with wheezing phenotypes at school age. METHODS: Children (N = 230) were recruited from the Asthma DEtection and Monitoring (ADEM) study. At preschool age [mean (SE): 3.3 (0.1) yr], pre- and post-bronchodilator Rint was assessed. EBC was collected using a closed glass condenser. Inflammatory markers (IL-2, IL-4, IL-8, IL-10, sICAM) were measured using multiplex immunoassay. Wheezing phenotypes at 5 yr of age were determined based on longitudinal assessment. Children were classified as: never (N = 47), early-transient (N = 89) or persistent wheezers (N = 94). RESULTS: Persistent wheezers had elevated levels of all interleukins at preschool age compared to children who never wheezed (p < 0.05). EBC markers did not differ between the persistent and transient wheezers. There was no marked difference in Rint between wheezing phenotypes. CONCLUSIONS: We demonstrated that 5 yr old children with persistent wheeze already had elevated exhaled inflammatory markers at preschool age compared to never wheezers, indicating augmented airway inflammation in these children.

Metabolomics of volatile organic compounds in cystic fibrosis patients and controls.

In cystic fibrosis (CF), airway inflammation causes an increased production of reactive oxygen species, responsible for degradation of cell membranes. During this process, volatile organic compounds (VOCs) are formed. Measurement of VOCs in exhaled breath of CF patients may be useful for the assessment of airway inflammation. This study investigates whether "metabolomics' of VOCs could discriminate between CF and controls, and between CF patients with and without Pseudomonas colonization. One hundred five children (48 with CF, 57 controls) were included in this study. After exhaled breath collection, samples were transferred onto tubes containing active carbon to adsorb and stabilize VOCs. Samples were analyzed by gas chromatography-time of flight-mass spectrometry to assess VOC profiles. Analysis showed that 1099 VOCs had a prevalence of at least 7%. By using 22 VOCs, a 100% correct identification of CF patients and controls was possible. With 10 VOCs, 92% of the subjects were correctly classified. The reproducibility of VOC measurements with a 1-h interval was very good (match factor 0.90 +/- 0.038). We conclude that metabolomics of VOCs in exhaled breath was possible in a reproducible way. This new technique was able to discriminate not only between CF patients and controls but also between CF patients with or without Pseudomonas colonization.

Sleep disturbances associated with periodic leg movements in chronic sarcoidosis.

BACKGROUND AND AIM OF THE WORK: Many sarcoidosis patients suffer from fatigue and sleep disturbances. Recently, it was demonstrated that obstructive sleep apnea (OSA) is rather common in sarcoidosis. Moreover, sheet intolerance and painful legs are frequently reported in sarcoidosis patients. These symptoms might interfere with sleep quality. METHODS: In order to determine the relationship between objective and subjective sleep disturbance full polysomnography, including leg EMG analysis, was performed in 46 chronic sarcoidosis patients indicating awakening unrefreshed in the morning. RESULTS: In 20 (44%) patients OSA activity [60% with PLM (n=12), 40% without (n = 8)] was demonstrated, while in 7 patients (15%) significant PLM without OSA were found. In 19 patients (42%) no OSA or PLM activity was present. Moreover restless legs (RLS) were reported by 52% of the patients (45% in OSA; 71% in PLM; 47% in others). Distribution of sleep stages and sleep fragmentation was comparable in all groups. In a healthy snoring control group (n = 102) a prevalence of PLM was found in 13.7% (17.8% in men; 3.4% in women), while RLS were only reported by 1.4% (men) and 6.9% (women). CONCLUSIONS: Sleep disturbance (OSA and/or PLM) and RLS were demonstrated in more than half of the studied sarcoidosis patients. A high prevalence of RLS or PLM (primary and secondary) has not been reported before in sarcoidosis. Further studies are needed to establish whether RLS, OSA and/or PLM might contribute to fatigue and whether fatigue complaints improve after treatment of RLS/PLM/OSA.