HOMA indices as screening tests for cystic fibrosis-related diabetes.

BACKGROUND: We assessed the diagnostic performances of homeostasis model assessment indices (HOMA) of ß-cell function (HOMA-%ß) and of insulin resistance (HOMA-IR) for cystic fibrosis related diabetes (CFRD) screening. METHODS: Data were collected from a prospective cohort of 228 patients with CF (117 adults and 111 children). Fasting insulin and glucose levels were measured to calculate HOMA-%ß and HOMA-IR. HOMA-%ß <100 indicated insulin secretion deficiency and HOMA-IR >1 insulin resistance. Both were used to calculate sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Two-hour oral glucose tolerance tests (2h-OGTT) defined CFRD. Analyses were conducted separately for children and adults. Performances of HOMA-%ß and HOMA-IR were calculated at inclusion, for each year of follow-up and for pooled data over the follow-up period. RESULTS: Sensitivity, specificity, NPV and PPV were respectively: 88%, 45%, 98% and 11% for HOMA-%ß and 42%, 48%, 91% and 6% for HOMA-IR in the pooled data of children; and 83%, 18%, 90% and 10% for HOMA-%ß, and 39%, 80%, 92% and 18% for HOMA-IR in the pooled data of adults. Combining HOMA-%ß and HOMA-IR did not improve performances. CONCLUSION: Within both age groups, HOMA-%ß <100 provided good sensitivity and NPV. HOMA-IR >1 had low sensitivity. Calculation of the HOMA-%ß could be an interesting first-line screening approach to exclude CFRD and thus avoid unnecessary OGTT in patients for whom value is ≥100. However, HOMA-%ß<100 does not support the diagnosis of CFRD and should be complemented by OGTT.

Impact of Coexistence Phenotype Between Staphylococcus aureus and Pseudomonas aeruginosa Isolates on Clinical Outcomes Among Cystic Fibrosis Patients.

Staphylococcus aureus (SA) is the major colonizer of the lungs of cystic fibrosis (CF) patients during childhood and adolescence. As patients age, the prevalence of SA decreases and Pseudomonas aeruginosa (PA) becomes the major pathogen infecting adult lungs. Nonetheless, SA remains significant and patients harboring both SA and PA are frequently found in the worldwide cohort. The overall impact of co-infection remains controversial. Furthermore, co-infecting isolates may compete or coexist. The aim of this study was to analyse if co-infection and the coexistence of SA and PA could lead to worse clinical outcomes. The clinical and bacteriological data of 212 Lyon CF patients were collected retrospectively, and patients were ranked into three groups, SA only (n = 112), PA only (n = 48) or SA plus PA (n = 52). In addition, SA and PA isolates from co-infected patients were tested in vitro to define their interaction profile. Sixty five percent (n = 34) of SA/PA pairs coexist. Using univariate and multivariate analysis, we confirm that SA patients have a less severe clinical condition than others, and PA induces a poor outcome independently of the presence of SA. Regarding co-infection, no significant difference in clinical outcomes was observed between patients with coexisting pairs and patients with competitive pairs. However, when compared to SA mono-infected patients, patients with coexisting pair presented higher frequency and length of hospitalizations and more exacerbations. We suggest that coexistence between SA and PA may be an important step in the natural history of lung bacterial colonization within CF patients.

The diagnosis of hypersensitivity to antibiotics is rarely confirmed by allergy work-up in cystic fibrosis patients.

Cystic fibrosis (CF) patients receive many antibiotic treatments for recurrent respiratory infections and frequently report antibiotic hypersensitivity reactions (HSRs). In this retrospective study, medical records of CF patients were reviewed to clarify the clinical features, the culprit antibiotics, and the prevalence of antibiotic HSRs in the CF population. From 601 CF patients, 95 suspected antibiotic HSRs occurred in 60 patients (prevalence of 10.0%). ß-Lactams were the most common inducers, but cotrimoxazole was also frequently involved. Seventy-six of 95 suspected HSRs were assessed by allergy workup including skin tests (43/76 reactions) and/or drug reintroduction as a full course of the culprit antibiotic (73 of 76 reactions). From the 43 suspected HSRs that were skin-tested, only three had positive skin tests and were not subjected to drug readministration. All the other 73 suspected HSRs received a full course of the culprit antibiotic: HSR symptoms recurred in 10 of 73 cases and therefore were considered as confirmed antibiotic HSRs; for the remaining 63 suspected HSRs that did not relapse after drug readministration, the diagnosis of antibiotic HSRs was excluded. In summary, 13 of 76 suspected HSRs were confirmed as antibiotic HSRs. The prevalence of suspected and confirmed antibiotic HSRs in CF patients appears similar to that reported in the general population. Of note, most of the antibiotic suspected HSRs are not confirmed after allergology workup. A complete allergy workup appears therefore crucial to make a correct diagnosis and to avoid unnecessary contraindication of major antibiotics.

Viral respiratory tract infections in young children with cystic fibrosis: a prospective full-year seasonal study.

BACKGROUND: Viral respiratory tract infections are common during early childhood. How they impact cystic fibrosis lung disease history in young children is poorly known. The principal aim of our study was to determinate respiratory tract infections frequency in this cystic fibrosis young population. Secondary outcomes were nature of viral agents recovered and impact of such infections. METHODS: We conducted a prospective cohort study of 25 children affected by cystic fibrosis and aged less than 2 years. Nasal samplings were taken systematically monthly or bimonthly with additional samples taken during respiratory tract infections episodes. Ten pathogens were tested by a combination of five duplex RT-PCRs or PCRs: influenza A and B, respiratory syncytial virus (RSV), metapneumovirus (MPV), rhinovirus/enterovirus (RV/EV)), coronavirus (HKU1, NL63, 229E and OC43), parainfluenza virus (1-4), adenovirus and bocavirus (Respiratory Multi-Well System MWS r-gene®, BioMérieux, Marcy l'Étoile, France). Cycle thresholds (CTs) were reported for all positive samples and considered positive for values below 40. Quantitative variables were compared using a nonparametric statistical test (Wilcoxon signed rank for paired comparisons). Pearson's correlation coefficient (r) was used to assess relationships between two variables. Statistical analyses were performed using SAS v9.4 (SAS Institute, Cary, NC, USA) or GraphPad Prism V6.00 (GraphPad Software, La Jolla, CA, USA). The significance level was set at 0.05. RESULTS: The mean age at inclusion was 9.6 ± 6.7 months. The patients had 3.4 ± 1.7 respiratory tract infections episodes per child per year. Forty-four respiratory tract infections (69%) were associated with virus: rhinovirus and enterovirus (RV/EV) were implied in 61% of them and respiratory syncytial virus (RSV) in 14%. Only one patient required hospitalization for lower respiratory tract infections. 86% of the patients were treated by antibiotics for a mean of 13.8 ± 6.2 days. RSV infections (n = 6) were usually of mild severity. CONCLUSIONS: Respiratory tract infections in young children with cystic fibrosis were of mild severity, rarely requiring hospitalization. Unsurprisingly, RV/EV were the most frequent agents. RSV-related morbidity seems low in this population. This raises the question of the usefulness of RSV preventive medication in this young population.

Diaphragmatic paralysis in young children: A literature review.

Diaphragmatic paralysis (DP) is a rare cause of respiratory distress in young children. In the first years of life, the main cause is phrenic nerve injury after cardiothoracic surgery or obstetrical trauma. DP usually presents as respiratory distress. Asymmetrical thorax elevation, difficulty weaning from mechanical ventilation, pulmonary atelectasis, and repeated pulmonary infections are other suggestive signs or complications. DP is usually suspected on chest X-ray showing abnormal hemidiaphragm elevation. Although fluoroscopy was considered the gold standard for DP confirmation, it has gradually been replaced by ultrasound, which can be done at the bedside. Some electrophysiological tools may be useful for a better characterization of phrenic nerve injury and chance of recovery. The management of DP is mainly based on clinical severity. In mild asymptomatic cases, DP may only require close monitoring. In more severe cases, adequate ventilatory support and/or surgical diaphragmatic plication may be needed. Electrophysiological tools may help clinicians assess the ideal timing for diaphragmatic plication.

Palivizumab prophylaxis in infants with cystic fibrosis does not delay first isolation of Pseudomonas aeruginosa or Staphylococcus aureus.

Respiratory syncytial virus (RSV) infections may worsen cystic fibrosis (CF) lung disease and favor Pseudomonas aeruginosa (Pa) or Staphylococcus aureus (Sa) acquisition, which is of particular importance in the youngest patients. We aimed to determine the effectiveness of PVZ on microbiological outcomes in young children with CF. We conducted a retrospective case-control study to compare these outcomes in children who systematically received PVZ (PVZ+; n = 40) or not (PVZ-; n = 140). One case was matched with at least three same-gender controls born the same year and month. Median (range) age at first Pa isolation was not statistically different between PVZ- (12.3 [3.8-32.6] months) and PVZ+ (10.4 [1.2-33.0] months; p = 0.953) patients. A similar trend was found for Sa (PVZ+: 6.4 [2.0-59.0] months; PVZ-: 3.8 [0.1-74.1] months; p = 0.191). The proportion of Pa isolations by 3 years of age did not differ between groups (PVZ+ 40% vs. PVZ- 41.4%), but this proportion was higher for Sa in the PVZ+ group (97%) than in the PVZ- group (85%; p = 0.001). Healthcare consumption and growth outcomes did not significantly differ between groups. CONCLUSION: Systematic PVZ use did not delay key pathogen acquisition in young children with CF. What is known: • Palivizumab is the only available monoclonal antibody against respiratory syncytial virus infection. • Whether or not it is useful in infants with cystic fibrosis remains controversial. What is new: • Palivizumab does not delay key pathogens (Pseudomonas aeruginosa, Staphylococcus aureus) first isolation in young children with cystic fibrosis. • Palivizumab does not reduce healthcare consumption or improve growth during the first 3 years of life of young children with cystic fibrosis.

Real-life acute lung function changes after lumacaftor/ivacaftor first administration in pediatric patients with cystic fibrosis.

The combination of lumacaftor and ivacaftor (LUM/IVA) has been reported to induce a mean acute absolute drop of -4.1% predicted forced expiratory volume in 1s (FEV1) after a unique administration in healthy subjects. The aim of the present study was to assess acute FEV1 changes after the first dose of LUM/IVA in CF patients. A total of 32 pediatric patients were included. Respiratory manifestations occurred in only 3 patients (9.4%), but FEV1 consistently decreased (-10.4±4.6%, range: -1.5; -21.8%). FEV1 only partially resumed after salbutamol inhalation. Patients with previously known significant reversible airway obstruction and low FEV1 were more at risk of FEV1 decrease.

Sensitivity and specificity of different methods for cystic fibrosis-related diabetes screening: is the oral glucose tolerance test still the standard?

BACKGROUND: Cystic fibrosis-related diabetes (CFRD) is a late cystic fibrosis (CF)-associated comorbidity whose prevalence is increasing sharply lifelong. Guidelines for glucose metabolism (GM) monitoring rely on the oral glucose tolerance test (OGTT). However, this test is neither sensitive nor specific. The aim of this study was to compare sensitivity and specificity of different methods for GM monitoring in children and adolescents with CF. METHODS: Continuous glucose monitoring system (CGMS), used as the reference method, was compared with the OGTT, intravenous glucose tolerance test (IGTT), homeostasis model assessment index of insulin resistance (HOMA-IR), homeostasis model assessment index of ß-cell function (HOMA-%B) and glycated haemoglobin A1C. Patients were classified into three groups according to CGMS: normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes mellitus (DM). RESULTS: Twenty-nine patients (median age: 13.1 years) were recruited. According to CGMS, 11 had DM, 12 IGT and six NGT, whereas OGTT identified three patients with DM and five with IGT. While 13 of 27 had insulin deficiency according to IGTT, there was 19 of 28 according to HOMA-%B. According to HOMA-IR, 12 of 28 had insulin resistance. HOMA-%B was the most sensitive method for CFRD screening [sensitivity 91% (95% CI), specificity 47% (95% CI) and negative predictive value 89% (95% CI)]. CONCLUSIONS: OGTT showed the weak capacity to diagnose DM in CF and should no longer be considered as the reference method for CFRD screening in patients with CF. In our study, HOMA-%B showed promising metrics for CFRD screening. Finally, CGMS revealed that pathological glucose excursions were frequent even early in life.

An impulse oscillometry system is less efficient than spirometry in tracking lung function improvements after intravenous antibiotic therapy in pediatric patients with cystic fibrosis.

A literature search identified one retrospective study on the responsiveness of impulse oscillometry (IOS) in pediatric patients with cystic fibrosis. The aim of this prospective observational study was to assess this property in an adequately powered study after intravenous antibiotic therapy (IVAT) administered for an acute episode of pulmonary exacerbation. Spirometry and IOS were done on the same day as the start and the end of IVAT. Data from 34 patients' of mean age 11.9 years (range, 5-17 years) were studied. The mean FEV1 at the start and at the end of the IVAT was 73.1 ± 23.8% (range, 23.4-122%) and 88.3 ± 21.3% (range, 29.4-131%), respectively. The mean relative change (mean ± SD) was 20.2 ± 14.2% for FEV1 (ΔFEV1 ), -21.9 ± 23.8% for reactance at 5 Hz (ΔX5) and -13.4 ± 18.9% for resistance at 5 Hz (Δ R5) (all P-values <0.05). There was a weak but significant correlation between ΔFEV1 and ΔX5 (r =-0.473; p = 0.01). The magnitude of improvement of ΔX5 was not statistically different between patients with normal versus abnormal lung function at the start of IVAT. Furthermore, using ΔX5 alone as an outcome measure of IVAT efficiency resulted in a significant improvement in 44% of the patients, while it was 79% with ΔFEV1 . These results indicate that IOS may track changes after IVAT, but that this improvement may be insufficiently evaluated using IOS alone.