Joint Annual Meeting of the Swiss Society for Allergology and Immunology and the Swiss Respiratory Society, Bern, April 17-19, 2013

2013 Respiration  
The Swiss Childhood Cancer Survivor Study investigates long-term effects of childhood cancer. Pulmonary toxicity is an important complication of anticancer treatment and recent studies have shown that pulmonary causes account second for the excess mortality risk in long-term childhood cancer survivors (standardised mortality ratio of 8.8). However, little is known about pulmonary morbidity in childhood cancer patients treated in the last two decades. In this national study, we compared
more » ... e of respiratory problems between childhood cancer survivors and their siblings. Methods: All survivors of childhood cancer in Switzerland, aged <16 years at diagnosis, who survived >5 years and were diagnosed between 1976 and 2005 received a postal questionnaire. As a control group, their siblings received the same questionnaire. We assessed respiratory morbidity (asthma, hay fever, sinusitis, pneumonia, chronic cough, chest wall abnormalities, lung fibrosis and emphysema) and respiratory consultations in survivors and siblings. Results: 1,567 survivors (response rate 74%) and 713 siblings (56%) returned questionnaires. Mean age at survey was 25.0 years (SD 6.9), 52.4% were males. Compared to siblings, survivors reported significantly more often to have had pneumonias (3.4% vs. 1.9%, p=0.03), recurrent sinusitis (4.1% vs. 2.4%, p=0.03), chest wall abnormalities (1.9% vs. 0.2%, p<0.001), pulmonary fibrosis (0.6% vs. 0.1%, p=0.01) and lung function consultations (13.6% vs. 5.8%, p<0.001) in the past 2 years. Hay fever (19.7% vs. 17.7%) and asthma (4.9% vs. 5.6%) were equally common. Conclusion: Young adult survivors of paediatric cancer had a similar prevalence of atopic disorders, but significantly higher occurrence of respiratory infections, pulmonary fibrosis and chest wall abnormalities than their siblings. High risk groups should be identified, who could profit from regular respiratory follow-up to prevent long-term chronic morbidity and early mortality. Introduction: Bronchopulmonary dysplasia (BPD) is characterized by structural alterations of lung periphery with well-defined consequences on ventilation distribution. Volumetric capnography (VC) has been used in adults to provide information on physiological deadspace and ventilation-over-perfusion status. The aim of this study was to assess the value of VC in describing ventilation inhomogeneity in infants with BPD. Methods: Lung function (tidal breathing and multiple breath washout) parameters from 54 healthy preterm infants and 31 infants with BPD were compared. Breath-by-breath expiratory capnograms were obtained over 100 tidal breaths by mainstream Abstracts Respiration 2013;85:523-623 524 capnography. The slopes of phases II (SII) and III (SIII) were calculated by linear regression on emprirically chosen intervals as follows: For SII between 5 and 40, 50, or 60% of the end-expiratory CO2 fraction (SII5-40%, SII5-50%, and SII5-60%), and for SIII between 40, 50, or 60 and 95% of the expiratory volume (SIII40-95%, SIII50-95%, and SIII60-95%). VC indices were compared between BPD and non-BPD infants and their relation with lung clearence index (LCI) was assessed. Results: All capnographic indices differed significant between the two groups. The SIII40-95% was associated with the highest between-groups difference (non-BPD 0.07 [0.05-0.10], BPD 0.13 [0.07-0.20]; P=0.002) and the best discriminatory ability (area under the ROC curve -AUC: 0.760). The SII5-60%/SIII40-95% ratio had a similar performance (AUC 0.738), whereas the AUC for the LCI was 0.539. VC indices were positively correlated with the LCI in the BPD group (Pearson: 0.501 for SIII40-95% and 0.593 for SII5-60%/SIII40-95% ratio [P<0.001]). Conclusions: The simpler VC method might be used as an alternative to the inert gas washout techniques for assessing ventilation inhomogeneity in infants with BPD. Introduction: We have recently shown that tobacco smoking and air pollution during pregnancy increase the risk for respiratory symptoms in the first year of life. The aim of this study is to assess whether or not breastfeeding modifies these harmful effects. Method: A prospective birth cohort study of 380 children provided the weekly information about the breastfeeding status, and incidence and severity of respiratory symptoms during the first year of the life. A generalized additive mixed model (GAMM) with quasi Poisson distribution was used to assess a potential impact of breastfeeding duration and exclusiveness on the development of respiratory symptoms in infancy. Results: The multivariable longitudinal analysis showed that the age modified the protective breastfeeding effect on the respiratory morbidity (p value for interaction <0.05). There was no interaction effect between breastfeeding and maternal smoking during the pregnancy. The effect of N02-air pollution levels during pregnancy on respiratory symptoms in the offspring was significantly modified by the breastfeeding status (p for interaction <0.05). Additionally, we observed the age-dependent effect of maternal Note: Percentages are based upon available data for each variable. Abbreviations: n, number. a Age-and sex-standardized numbers and percentages are given for siblings. b Column percentages are given. c p-value calculated from chi-square statistics comparing survivors and siblings. d Problem is still existing. e Lasting for longer than three month. Abstracts Respiration 2013;85:523-623 525 smoking during pregnancy on the frequency of respiratory symptoms in infancy (p value for interaction <0.001). Conclusion: Breastfeeding protects children against respiratory symptoms during the first year of life, but the effect is modified by age. The effect of air pollution during pregnancy is modified by the breastfeeding status. Introduction: Virus-associated pulmonary exacerbations, most predominantly caused by rhinoviruses, contribute to cystic fibrosis (CF) morbidity. However, there are only few therapeutic options to treat virus-induced CF pulmonary exacerbations. Recent evidence suggests that the macrolide antibiotic azithromycin has antiviral properties in rhinovirus-infected primary human bronchial epithelial cells. We hypothesized that azithromycin induces antiviral mechanisms in primary CF airway epithelial cells. Methods: Primary nasal and bronchial epithelial cells from 8 CF children (median [range] age: 8.83 [2.75-13.5] years) and from 9 healthy control children (8.25 [2.17-15.33] years) were pretreated with azithromycin and infected with rhinovirus (RV16, major group and RV1B, minor group). RV16 and RV1B replication was measured by RT-qPCR. Results: After azithromycin pretreatment, RV1B replication was 7-fold reduced in non-CF bronchial cells (p<0.01) and reduced by half in CF bronchial cells (p<0.05). RV1B replication after azithromycin pretreatment was reduced, but not significantly in CF nasal cells. There was a trend towards lower RV16 replication after pretreatment with azithromycin in non-CF bronchial cells. However, azithromycin pretreatment did not affect RV16 replication in CF bronchial and nasal cells. Conclusion: Azithromycin pretreatment reduces rhinovirus replication in primary paediatric CF and control airway epithelial cells. This study highlights the potential of azithromycin as a novel therapeutic option to treat rhinovirus-induced CF pulmonary exacerbations. Background: Newborn screening (NBS) for cystic fibrosis (CF), based on immunoreactive trypsinogen (IRT) and 7 most common CFTR mutations, was introduced in Switzerland on January 1st 2011. In the pilot phase, we also compared the performance of two sweat test methods for diagnosing CF in the NBS. Methods: All children with a positive screening result were referred to a CF center for confirmatory testing with: a) the Macroduct test (chloride; at least 15-30ml sweat required); and b) the Nanoduct sweat test system (conductivity; at least 3-5ml sweat required). If sweat test results were positive, borderline or inconclusive, an extensive DNA analysis was performed. Results: Within two years, 162 children were screened positive and further investigations in a CF center were needed. In 49 children the diagnosis of classic CF could be confirmed, and in 12 children an equivocal CF was made. Eighty-eight children had negative investigations for CF, and 13 children were not yet fully investigated. In 141 children, all details of the investigations were available and included in our analysis. The 141 children were seen in a CF center at a median age of 25 days. The Macroduct was attempted in 121 children (86%), the Nanoduct in 136 children (96%). A reliable test result was available in 74% (89/121) for the Macroduct and 86% (117/136) for the Nanoduct. In 81 children both sweat tests could be performed, while in 36 only the Nanoduct and in 8 only the Macroduct was feasible. In 16 children none of the two sweat tests could be performed, and confirmation or exclusion of CF was based on DNA analysis and clinical assessment alone. Conclusions: In this 2 years pilot study, the Nanoduct sweat test system showed a better feasibility for use in newborns compared to the Macroduct test, mainly because it needs a lower sweat volume. Analysis of a larger dataset will allow to compare sensitivity and specificity of the two tests for the final CF diagnosis. Abstracts Respiration 2013;85:523-623 Background: In children with cystic fibrosis (CF) small airway disease occurs early in life. Introduction of CF in the newborn screening (NS) enables early diagnosis. Since recent lung function data in CF infants at the age of 3 months have been shown to be abnormal we wanted to examine whether lung function is already abnormal shortly after birth in infants with CF diagnosed by NS. Methods: We performed multiple-breath washout (MBW) using 4% sulfur hexafluoride and tidal breathing measurement during non-REM sleep in 23 infants with CF, aged median (range) 6.5 (3.9-12.6) weeks, and compared it to a previously reported equipment and tracer-gas specific normative data population of 292 healthy infants, aged median 5.1 (3.6-8.7) weeks (Fuchs et al, ERJ 2011). We compared LCI and functional residual capacity (FRC) of MBW and the following tidal breathing parameters: tidal volume, respiratory rate, minute ventilation, mean and peak tidal inspiratory and expiratory flow and the ratio of time to peak tidal expiratory flow and expiratory time. Results: Compared with controls, and after adjustment for body weight and age, LCI was similar in infants with CF (mean difference (95% CI): 0.37 (-0.10 to 0.83) z-scores, p=0.12), as was FRC (mean difference (95% CI): 0.36 (-0.09 to 0.82) z-scores, p=0.12). No difference was found for any of the tidal breathing parameters between CF and controls. Only one (4%) infant with CF had elevated LCI (> 1.96 z-scores), while none of the CF infants showed elevated FRC (> 1.96 z-scores). Conclusions: CF infants shortly after birth showed normal LCI values and thereby no sign of ventilation inhomogeneity. Since also FRC and tidal breathing parameters were in a normal range, this seems to reflect the still undamaged state of small airways. This highlights the importance of early therapy to maintain normal lung function as long as possible. Introduction: Necrotizing pneumonia (NP) is an increasing complication associated with pleural empyema. However, specific risk factors, clinical features and outcome are not well-known. We aimed to compare children presenting with empyema with or without NP. Methods: We retrospectively included all children with a diagnosis of empyema, hospitalized from January 2005 to December 2011. NP was assessed on CT scan. We recorded age, gender, clinical features, biological and radiological findings, pleural tap, surgery, antibiotics, oxygen, length of stay, and outcome. Results: We included 23 children with isolated empyema and 24 with concomitant NP. Median age was 3.74 and 3.76 years, respectively. Main symptoms were fever, cough, lethargy, abdominal and chest pain. 18/23 and 16/24 children showed leukocytes up to 10G/l. Median C-reactive protein was 200 and 199mg/l, respectively. Pathogens were mostly Streptococcus pneumonia (14/23; 20/24) and staphylococcus aureus (3/23; 0/24). All patients required intravenous antibiotic (median duration: 11 and 12 days, respectively). 22/23 and 24/24 underwent further oral antibiotic (median duration: 21d). 16/23 and 9/24 needed oxygen (median (range) duration: 3 (0-10); 0d (0-40), respectively). Median (range) length of stay was 13 (7-42) and 15d (8-140), respectively. Complications occurred in 3/23 children without NP (pneumothorax, bronchopleural fistula, pneumotocele) and 4/24 with NP (3 bronchopleural fistula including 1 leading to lobectomy, multiple chest tubes). After 6 weeks, X-ray was still abnormal in all patients. 4/23 and 4/24 had functional follow-up: normal (3 patients in both group), obstructive (1 without NP) and restrictive syndrome (1 with NP). Conclusion: No difference in clinical course, treatment and complications were observed, between children with or without risks factors. CT scan might be questionable if just done to diagnose NP. However, long term follow-up may help in defining potential functional sequelae. Abstracts Respiration 2013;85:523-623 Background: Nocturnal hypoxemia and sleep apnea are common in patients with pulmonary hypertension (PH) and impair well-being. Nocturnal oxygen therapy (NOT) and acetazolamide may enhance exercise performance by improving PH through preventing nocturnal hypoxemia and periodic breathing. We tested whether NOT or acetazolamide improve the walk distance and quality of life in patients with precapillary PH associated with sleep disturbed breathing. Methods: Patients with PH (class II and IV) on optimized pharmacological therapy with mean nocturnal oxygen saturation <90% or >10/h desaturation dips >4% were recruited. Patients received NOT (3L/min), acetazolamide (2x250 mg/d) and sham oxygen (placebo) for 1 week in a randomized, double-blind, crossover protocol with 1 week washout periods. Main outcomes at end of treatment periods were the 6 min walk distance and SF-36 physical component summary, additional outcomes were derived from polysomnography, echocardiography, questionnaires and vigilance tests. Results: Medians (quartiles) of 6 minute walk distance on NOT, acetazolamide and placebo were 480m (390;528), 440m (368;468), 454m (367;510), respectively, P<0.001 ANOVA; median difference (95% CI) NOT vs. placebo +25 (3 to 46); median difference acetazolamide vs. placebo -9 (-34 to 17). SF-36 quality of life was similar on NOT, acetazolamide and placebo. Right ventricular fractional area change was greater on NOT compared to placebo. Conclusions: In PH patients with sleep disordered breathing NOT improves the 6 min walk distance compared to placebo already within one week. In contrast, acetazolamide has no beneficial effect on exercise performance. Therefore, NOT is promising as a long-term treatment for PH patients with nocturnal hypoxemia or sleep apnea. 528 sures included, Provent TM versus placebo Provent TM : OSA severity assessed by ODI/AHI from in-hospital sleep studies, and the Epworth sleepiness score. Comparisons were assessed by regression analysis on a per protocol basis. Results: Baseline characteristics of the three randomised groups are shown in table 1. 63 patients were included in the per protocol analysis. OSA recurred in both the Provent TM (ODI: 35.8 SD17.4) and placebo-Provent TM (ODI: 28.2 SD18.3) groups, and there was no significant difference in ODI, AHI and ESS between Provent TM and placebo-Provent TM at two weeks (mean difference ODI +7.5, 95%CI -3.9 to +19.0, p=0.19; AHI +3.4, 95%CI -7.2 to +14.0, p=0.52; and ESS -1.4, 95%CI -4.1 to +1.4, p=0.33). Conclusions: We have been unable to demonstrate a therapeutic effect of Provent TM versus placebo Provent TM in patients with OSA already on CPAP, who have their treatment withdrawn for two weeks. Thus Provent TM cannot be recommended as an alternative short-term therapy for patients on CPAP with originally moderate-to-severe OSA.
doi:10.1159/000350374 fatcat:vtrr2vkbn5gupj3p44ybn7csku