Véronique Nève

Natural evolution of weight status in Duchenne muscular dystrophy: a retrospective audit

The life expectancy of patients with Duchenne muscular dystrophy (DMD) has increased. A cross-sectional study of DMD patients showed that 54 % of 13-year-old patients are obese and that 54 % of 18-year-old patients are underweight. We aimed to describe the natural evolution of weight status in DMD. This retrospective multi-centre audit collected body-weight measurements for seventy DMD patients born before 1992. The body-weight:age ratio (W:A) was used to evaluate weight status in reference to the Griffiths and Edwards chart. At the age of 13 years, 73 % were obese and 4 % were underweight. At maximal follow-up (age 15-26 years, mean 18·3 (sd 2·3) years), 47 % were obese and 34 % were underweight. Obesity at the age of 13 years was associated with later obesity, whereas normal weight status and underweight in 13-year-old patients predicted later underweight. A W:A ≥ 151 % in 13-year-old patients predicted later obesity, and a W:A ≤ 126·5 % predicted later underweight. Our audit provides the first longitudinal information about the spontaneous outcome of weight status in DMD. Patients (13 years old) with a W:A ≥ 151 % were more likely to become obese in late adolescence, but obesity prevented later underweight. These data suggest that mild obesity in 13-year-old DMD patients (W:A between 120 and 150 %) should not be discouraged because it prevents later underweight.

Sniff nasal inspiratory pressure in the longitudinal assessment of young Duchenne muscular dystrophy children

Traditional measures of respiratory function in children with Duchenne muscular dystrophy (DMD) are based on maximal inspiratory pressure (PImax) and vital capacity (VC). Sniff nasal inspiratory pressure (SNIP) measurements are easily performed by young children with neuromuscular disorders. The clinical value of SNIP in the longitudinal assessment of respiratory weakness remains to be assessed. The objective of the present study was to assess longitudinally the changes in SNIP, PImax and VC with age in DMD children. We hypothesised that their longitudinal assessment would show an earlier decline in SNIP than VC. A 3-year, prospective follow-up, at 6-month intervals of, 33 steroid-naïve, 5–20-year-old DMD patients was analysed using a linear mixed model. SNIP measurements were reliable (within-session coefficient of variation 8%). SNIP and VC increased until 10.5 and 12.5 years of age, respectively, and declined thereafter, while PImax did not change with age. SNIP was an earlier marker of decline in respiratory muscle strength (at 10.5 years) than VC (at 12.5 years) in young DMD patients. SNIP longitudinal assessment is useful in the detection of inspiratory strength decline in young DMD patients when VC values remain within normal values and as an outcome measure in clinical trials for emerging therapeutics in young DMD patients from the age of 5 years. Earlier sniff nasal inspiratory pressure than vital capacity decline in follow-up of Duchenne muscular dystrophy children http://ow.ly/mn24K

Quantification of shape of flow‐volume loop of healthy preschool children and preschool children with wheezing disorders

The earliest change associated with airflow obstruction in small airways is reflected in a concave shape on the maximum expiratory flow‐volume loop (MEFVL). The shape of the MEFL changes with age but reference values for curvilinearity indices (CI) for preschool children have not been published. We aimed to describe the normal curvilinearity of healthy preschool MEFVL by CI (the β angle and the ratio of maximum expiratory flow when 50% of forced vital capacity remains to be expired/peak expiratory flow (MEF50%/PEF)) and to test their capacity in detecting concavity in preschool children with wheezing disorders.

Global Lung Function Initiative reference equations better describe a middle-aged, healthy French population than the European Community for Steel and Coal values

Spirometry plays a pivotal role in the clinical evaluation and management of respiratory diseases. Pulmonary function varies with age, height, sex and ethnicity, and test results need to be compared with predicted values and lower limits of normal (LLN) and upper limits of normal (ULN), that are appropriate for the individual being tested [1]. The European Community for Steel and Coal (ECSC) first published reference spirometric values for healthy non-smokers in 1983 based on a collation of regression equations [2]. In 2012, the Global Lung Function Initiative (GLI) presented prediction equations derived from measured values of a large population [1]. These newer statistical procedures provided us for the first time with a single equation for ages from 3 years through to 95 years. Measured values are converted to z-scores which describe how many standard deviations a measured value differs from the predicted value and these are independent of sex, age and height. GLI reference equations better describe a middle-aged, healthy French population than the ECSC values http://ow.ly/xF773022Xhy

The lung is involved in juvenile dermatomyositis.

Juvenile dermatomyositis (JDM) is the main cause of chronic idiopathic inflammatory myopathy of autoimmune origin in children. The aim of this multicenter prospective study was to describe respiratory status and treatment of children followed for JDM.

Reference ranges for shape indices of the flow-volume loop of healthy children.

The concavity of the descending limb of the maximum expiratory flow‐volume loop (MEFVL) is the earliest change associated with airflow obstruction in small airways (ATS/ERS Task Force). The shape of the MEFVL changes with age but there are no reference values for shape indices for preschool and school children. Objectives: To define pediatric reference values for spirometric data and 3 shape indices of MEFVL: 2 geometric indices: the β angle i.e., the angle between the first ½ part and the 2nd part of the MEFVL and the forced expiratory flow after 50% of the forced vital capacity (FVC) has been exhaled/peak expiratory flow (FEF50/PEF) ratio; and a ratio that describes relative growth between airway and lung parenchyma, the forced expiratory flow between 25 and 75% of FVC/FVC ratio (FEF25–75/FVC ratio). Methods: Data were obtained from 446 Caucasian children (2.5 to 15‐year‐old). The lambda, mu, sigma method was applied. Results: References for spirometric parameters and 3 shape indices. The geometric indices decreased with age from 3 years of age (mean β angle was 215° and FEF50/PEF ratio was 0.82) until 8 years of age (mean β angle was 191° and FEF50/PEF ratio was 0.60) and then remained constant. The FEF25–75/FVC ratio also decreased with age. Sex was a significant determinant for FEF25–75/FVC ratio predicted values. Conclusions: This study provides standard reference equations for indices of mid‐expiratory flows in children and we suggest using the FEF50/PEF index. Pediatr Pulmonol. 2015; 50:1017–1024.

Utility of measuring FEV0.75/FVC ratio in preschoolers with uncontrolled wheezing disorder

Uncontrolled wheezing disorder is common in preschoolers and disease control assessment is challenging as parents frequently overestimate the extent to which their childs disease is controlled. This is the first study of forced expiratory volume in t s (FEVt)/forced vital capacity (FVC) ratio measurements (i.e. FEV1/FVC, FEV0.75/FVC and FEV0.5/FVC) in wheezy preschoolers in relation to disease control. Our objective was to evaluate whether FEVt/FVC ratios less than the lower limit of normal (LLN; z-score <−1.64) were associated with uncontrolled wheezing disorder in preschoolers. Valid FVC, FEV1, FEV0.75 and FEV0.5 values were obtained in 92 healthy and 125 wheezy (62% uncontrolled) children (3–5 years). Associations between spirometry value <LLN, disease classification (healthy/wheezy) and disease control classifications (controlled/uncontrolled disease) were estimated using logistic regression. FEV0.75/FVC or FEV0.5/FVC ratios <LLN were associated with wheezing disorder (OR 9.78, 95% CI 3.70–25.88 and OR 6.64, 95% CI 2.24–19.66; all p<0.001). Only an FEV0.75/FVC ratio <LLN was associated with uncontrolled wheezing disorder (OR 2.53, 95% CI 1.12–5.68; p=0.025). FEV0.75/FVC ratio is a useful surrogate outcome index to evaluate the control of the wheezing disease of preschoolers. FEV0.75/FVC ratio values <LLN are associated with uncontrolled disease in preschool children with wheezing disorders http://ow.ly/Zl3Sh

Earlier decline in sniff nasal inspiratory pressure than peak expiratory flow in children with Duchenne muscular dystrophy

To the Editor: In Duchenne muscular dystrophy (DMD), progressive weakness of the respiratory muscles leads to a restrictive ventilatory defect contributing to early morbidity and mortality. We have recently shown by a longitudinal assessment of vital capacity and sniff nasal inspiratory pressure (SNIP) in young DMD children that SNIP was an earlier marker of decline in respiratory muscle strength than vital capacity [1]. However, early involvement of the expiratory muscles is a characteristic feature of DMD, as shown by the earlier decrease in expiratory ( P Emax) than inspiratory maximal pressure ( P Imax) [2]. In the absence of bronchial obstruction, peak expiratory flow (PEF) reflects maximal expiratory muscle strength [3]. In patients with respiratory weakness, PEF is reduced and correlated with P Emax [4]. Recently, it was shown that DMD patients on a 1-year idebenone treatment improved in expiratory muscle strength (evaluated by PEF) while patients on placebo deteriorated [5]. No difference between treatments groups were observed for measures such as vital capacity [6], suggesting that PEF could be used as an outcome parameter to assess the effect of early therapeutic interventions on respiratory muscle strength in DMD. As candidate drugs for the treatment of DMD enter clinical trials, it is important to determine the natural evolution of pulmonary function parameters that could be used as outcome measures for efficacy studies in DMD children. However, to our knowledge, there are no data on the natural evolution of PEF in young DMD children and there is no information on the age of PEF decline compared with the age of SNIP decline. …