Health-related quality of life of Spanish children with cystic fibrosis

Children with CF, 6–17 years of age, previously diagnosed by means of a genetic test and treated at the Hospital Niño Jesús or the Hospital La Paz in Madrid, were invited to participate. All children had CF of low-to-moderate severity and stable clinical condition. Children with the following conditions were excluded from the study: severe lung deterioration, as defined by FEV₁ below 40% of expected, hospitalization within the previous 3 months, or having Burkholderia cepacia infection. All children and one of their parents or caregivers provided written informed consent prior to the study. Ethical approval for this study was obtained from the Ethics Committee of the Hospital Niño Jesús in Madrid (approval number 006-09). The study was performed in accordance with the Declaration of Helsinki.

Body weight was measured using a digital balance (Seca, Madrid, Spain) to the nearest 0.1 kilogram (kg), with the children wearing no shoes. Body height, without shoes, was measured using a stadiometer (Seca, Madrid, Spain) with the children in standing position, their heels and head against the wall and their faces in a horizontal plane, to the nearest 0.1 cm. Body mass index was calculated by dividing weight in kg by height in metres (m) squared (kg/m²). Body mass index percentiles were determined using the Centre of Disease Control BMI-for-age charts for boys and girls [17]. Additionally, triceps, abdominal, suprailiac, and thigh skinfolds were measured with a calliper (Holtan Crymych, United Kingdom). Body fat percentage was estimated using the equation described by Jackson and Pollock [18].

Physical activity (PA) was assessed using accelerometers (Actigraph 7164, Manufacturing technology Inc., Shalimar, Florida, USA), following the protocol of Ortega et al. [19], and the data on PA were processed using MAH/UFFE (version 1.9.0.3). Participants were instructed to wear the accelerometer on their lower back attached by an elastic belt during all waking hours. Since the monitors were not waterproof, participants were asked to take them off while bathing or swimming. Count data were stored each minute. Each sequence of 10 or more zero counts was deleted, assuming that the accelerometer was not worn at that interval. At least 5 days of recording including 2 weekend days, with a minimum of 10 h of registration per day, were necessary to be included in the study. Levels of PA were expressed as counts per minute.

Pulmonary function was determined according to the spirometry protocol by the American Thoracic Society [20], and we calculated the percentage of FEV₁ expected. As an additional indicator of pulmonary function, peak minute ventilation (VE_peak; litres [l]/min) was measured. The VO_2peak (ml/kg/min) was determined using open-circuit spirometry and paediatric face masks during a graded treadmill test (Technogym Run Race 1400HC; Gambettola, Italy). Gas exchange was measured breath-by-breath (Vmax 29c; Sensormedics; CA, USA). The test was performed after one familiarization session. According to the protocol of San Juan et al., treadmill speed began at 1 km/h, with an inclination of 5%. Every 15 s, the speed and inclination were increased by 0.1 km/h and 5%, respectively [21]. The test was terminated upon volitional fatigue or when the child showed loss of ability to maintain the required workload.

Dynamic upper- and lower-body muscle strength (kg) were measured using a seated bench, seated lateral row, and seated leg press machine, designed for use by a paediatric population (Strive Inc. Philadelphia, USA). We determined the six-repetition maximum (6RM) lifting ability, within the full rage of motion, in each muscle group, that is, pectoral, dorsal, and legs, until momentary muscular exhaustion. The protocol for these tests has been described in detail by San Juan et al. [21]. These tests showed a high reliability (all intra-class correlation coefficients for test–retest: R ≥ 0.98, P < 0.01).

Functional mobility was assessed with the 3 m Timed Up and Go (TUG 3 m) test: the time (s) needed to stand up from a chair, walk 3 m, turn around, return to the chair, and sit down was recorded. Children also performed the Timed Up and Down Stairs (TUDS) test, in which the time (s) to ascent and descent 12 stairs was recorded. In both tests, performance time was measured to the nearest 0.1 s. The aforementioned functional mobility tests are reliable (R = 0.99, P < 0.01) and valid in paediatric patient populations [22].

The HRQOL was determined with the Spanish version (1.0) of the CF questionnaire (CFQ-R). The CFQ was originally developed by Henry et al. [23] and translated, validated, and partly revised by Modi and Quittner [24]. Three versions of the CFQ-R exist: for children aged 6–13 years, for parents of children aged 6–13 years, and for adolescents and adults aged 14 years and over. The 6–11-year-old group completed the CFQ-R by means of an interview, whereas the 12–13-year-old group completed the same CFQ-R themselves. Adolescents aged 14 and over completed the CFQ-R version 14+. In the majority of cases, the parent was present during the completion of the questionnaire by his/her child. In order to get insight into the parents’ perception of their children’s HRQOL, parents or caregivers of all 6–13-year-old children were asked to fill the parents’ version of the CFQ-R. In the analyses of the associations between HRQOL and the physical-fitness-related variables, we used the eight domains that the age 6–13 and age 14+ groups had in common, that is, physical functioning, emotional functioning, social functioning, treatment burden, eating disturbances, body image, respiratory symptoms, and digestive symptoms. In the analyses of parent–child agreement, we used the seven domains that children aged 6–13 years and parents had in common, that is, all of the abovementioned, except for social functioning. Response choices of the CFQ-R included ratings of frequency or likelihood on four-point scales. Raw scores were converted into standardized scores (0–100) for each of the scales, with higher scores indicating better HRQOL. For example, the following statements were verified: ‘In the past 2 weeks you were able to run, jump and climb as you wanted’ (1 = very true, 4 = not at all true; domain of physical functioning), ‘Let us know how often in the past two weeks you coughed during the day’ (1 = always, 4 = never; domain of respiratory symptoms), ‘During the past 2 weeks, doing your treatments bothered you’ (1 = very true, 4 = not at all true; domain of treatment burden). Regarding the internal consistency of the Spanish CFQ-R 14+, Cronbach’s α is ≥0.70 for most domains except for digestive symptoms (0.31) and treatment burden (0.57) [9]. As for test–retest reliability, Spearman’s r oscillates between 0.49 and 0.95 [9]. The validity of the Spanish version of the CFQ-R 6–13 has not been investigated yet. In the English version for children aged 6–13, Cronbach’s α for internal consistency is ≥0.60 for all scales, except for treatment burden (0.44). Furthermore, the CFQ-R 6–13 has demonstrated adequate content and discriminant validity, and minimal floor and ceiling effects [24].

Data were analysed using SPSS, version 15.0 (Chicago, IL, USA). For addressing the first objective, we included all children, aged 6–17 years, with complete data on all variables. Values are presented as means and standard deviations (SD), medians and inter-quartile ranges. For comparing differences between groups, parametric or non-parametric tests were used as appropriate. For the regression analysis, a normal distribution of the residuals of the variable was a prerequisite. To investigate the associations of each domain of HRQOL with BMI percentile, body fat, PA, pulmonary function, cardiorespiratory fitness, dynamic muscle strength, and functional mobility, simple linear regression analyses were performed. Variables that showed an association with a P value <0.1 in the simple linear regression model were tested for association in a multiple linear regression model, using a stepwise forward procedure. The threshold of 0.1 was used for the selection of variables, to prevent potentially relevant variables from being missed in the multiple linear regression model. In the final—multiple linear regression—model, only the associations with a P value <0.05 were considered statistically significant. All multiple linear regression analyses were adjusted for sex and age by entering these two variables first. Given the small sample size, the results of multiple regression analysis should be considered exploratory.

As to the second objective, data on the seven domains of HRQOL reported by children aged 6–13 and their parents were used. The differences in median scores between parents and children were examined by means of a Wilcoxon signed ranks test. The correlations between child and parent reports on each domain of HRQOL were examined using intra-class correlation (ICC) analysis. The ICC was used instead of Spearman’s or Pearson’s correlations, as it corrects for systematic differences between raters. An ICC <0.4, =0.4–0.6, =0.6–0.8, or >0.8 was considered as an indicator of poor, moderate, high, or excellent agreement, respectively [25].