A recent statement of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) on pulmonary rehabilitation highlights the great progress that has been made in evidence-based support for pulmonary rehabilitation in the management of patients with chronic respiratory disease [1]. Rehabilitation programs are comprehensive interventions which have been shown primarily for individuals with chronic obstructive pulmonary disease (COPD), to reduce dyspnoea, increase exercise performance, improve health-related quality of life (HRQL), and to reduce effectively health care costs [1].

Although it has become clear that patients regardless of the type of chronic respiratory disease, experience a substantial morbidity from secondary impairments, like peripheral muscle, cardiac, nutritional, and psychosocial dysfunction, as well as suboptimal self-management strategies, comparable data are barely available in patients with cystic fibrosis. In fact, in the mentioned ATS/ERS statement this disease entity is mentioned only twice [1]. Thus it is evident that for cystic fibrosis patients up-to-date evaluated and structured rehabilitations programs have not yet been developed. Reasons for this may include that cystic fibrosis patients only represent a small group of subjects, include a broad age range from infancy to adulthood, and most importantly the bad experiences made previously in so-called summer camps. These were holiday-like rehabilitation efforts for cystic fibrosis patients, which were not infection controlled and cohorted considering pulmonary pathogens. In these camps a significant risk of microbial cross infection between patients was demonstrated [2-8]. Nevertheless, rehabilitation programs in cystic fibrosis have a long standing tradition in some European countries [9-13]. These programs absolutely differ from the so-called summer camps, especially because of taking very carefully into account hygiene aspects, among many other factors. They are perceived as helpful from a patient’s perspective, as they appear to improve health status, specific physiotherapeutic and psychosocial skills, and disburden families with small children and single adults. Many physicians share this attitude; the programs are paid by the national state insurance system every 4 years, in exceptional cases depending on individual state of health every 1-2 years.

Unfortunately very little is known on the quality and safety of these programs. For a full positioning of such programs and more importantly for their future development into definite evidence based pulmonary rehabilitation for CF patients according to state of the art knowledge, a description of the current outcome of these programs is desirable.

We therefore evaluated the effect of rehabilitation programs at different sites and in an unbiased manner by comparing data on the clinically most important measurements concerning lung function and bodyweight before and after the programs. Additionally, the amount of missing data from rehabilitation site reports was analysed.

We retrospectively studied the rehabilitation related data from all consecutive subjects at our center processed by one single social worker who had participated in the rehabilitation program in Israel during the seasons 1999/2000 to 2003/2004 and the data from all subjects who participated in German/Swiss rehabilitation programs during a similar time period. The patients from the German/Swiss rehabilitation centres were combined to one group, in order to compare the results to the Israel rehabilitation program which took place in a totally different climate during winter time in Germany and Switzerland.

The overall completeness of the reports on quantitative key outcomes was clearly low in all rehabilitation programs investigated. Based on the data retrieved, both the Israel and the German/Swiss rehabilitation programs significantly improved overall lung function and weight of patients with cystic fibrosis of all age groups. At the Israel site FVC and oxygen-saturation improved, whereas at the German sites FEV₁ did. While lung function improved early on and then remained stable, the gain of body weight was sustained and proportional to the length of the stay. Inter-individual responses were much more pronounced than variability within subjects. There were no differences in the extent of the rehabilitation effects at Israel and German/Swiss sites, as shown by matched comparisons.

This is to our knowledge the largest systematic analysis of rehabilitation programs in patients with cystic fibrosis published so far. One of the strengths of this study is that it included all patients of a predefined group of subjects from our centre that participated in the mentioned rehabilitation activities. Thus a selection bias was avoided and with the “intention to treat analysis” approach, we were able to obtain a “real life” assessment of the outcome. Since complete and unbiased up-to-date evaluation by the rehabilitation program providers are not published in an accessible way, we decided to do this analysis from the perspective of a site submitting patients, accepting potential disadvantages of this approach. First, the submitting centre did not always receive the appropriate medicinal and psychosocial information necessary to judge on the success or failure for a particular patient, including missing data for key variables before and after the program, reports on exacerbations during a stay, data on other untoward events or on psychosocial problems. Second, the precise nature and frequency of interventions performed by the patients often remained unclear. We can only infer from the procedures stated in the program description provided by the rehabilitation centres what might be offered to the patient. Third, the results we present here, only concern cystic fibrosis patients from our centre and results of patients from other submitting sites are unknown. However, the major advantage of this approach is an overview on the outcome of the current rehabilitation programs currently utilized in Germany, Switzerland and Israel. Extra attention was put on the quality of the reports received from the rehabilitation sites, because values on key measurements often were missing in these reports.

The study clearly demonstrated that one of the apprehensions made before the study was true, i.e. that the quality of many of the reports received from the rehabilitation sites was inappropriate; clearly it cannot be tolerated that in up to more than 50% of the critical variables, e.g. lung function, describing the impact of an individual rehabilitation, are not given in the reports of some rehabilitation sites. We interpret this result as one strength of this study to clearly visualize missing data for the first time in a study on rehabilitation programs in cystic fibrosis, although of course the missing data somewhat weaken the value of the nevertheless large data set. For the future therefore it will be essential to improve data reporting on the part of rehabilitation sites.

Having these limitations in mind, some inferences can be drawn from this retrospective analysis. We show for two key indicators of health in cystic fibrosis patients, both, lung function and weight, an overall significant improvement by these rehabilitation programs. We determined the extent and variability of changes that can be expected and also the fraction of subjects not responding favorably. Of interest there was a steady time dependent improvement in body weight, which was demonstrated independently in two cohorts. Weight is an indicator not only of overall fitness but also an independent risk factor for survival in cystic fibrosis patients [15] similarly as FEV₁ [16]. Due to the nature of our study and mainly because of the large amount of missing data reported, we also cannot analyze which intervention(s) were performed in which individual patients and which were responsible for the changes observed. Overall the results clearly demonstrate that rehabilitation programs as assessed here may objectively be helpful in a substantial fraction of cystic fibrosis patients and that they have the potential to be further developed into high quality and evidence based programs, which must be warranted by prospective evaluation.

Previous small cohort studies have already assessed the physiological impact of rehabilitation on nutritional status [17] and, at the Israeli site, on exercise capacity, which improved [10], and on pulmonary function and weight gain during and up to 3 months after the three week rehabilitation [18]. The results were in concordance with our findings. Unfortunately the latter study also had a retrospective design and the completeness of the sample is not known. Problems with selection bias must also be considered in the study on the impact of the rehabilitation program on quality of life indices [11]. In that study an unknown number of patients participating in rehabilitation programs at various sites over undetermined time periods were combined. Interestingly, the quality of life improved for a sustained period of at least two months after the end of the intervention [11]. A study of the site in Davos, Switzerland, which was also included in our study, reporting on 13 Israeli patients with cystic fibrosis, did not find improvement of lung function; however exercise tolerance and weight improved significantly [12]. The authors of the latter study argued for a reinstitution of rehabilitation activities for patients with cystic fibrosis, if special care is taken to prevent cross-infection.

The hygiene aspect is the key for any future development of up-to-date rehabilitation programs in cystic fibrosis. Our study did not target this issue. We did not systematically investigate our patients directly before and after a stay; however patients were only sent to those rehabilitation sites who were sensitized for the hygiene issue as demonstrated by cohorting all their patients on a time and space basis according to their microbiological status and enforcing hygiene rules in personal contact and inhalation equipment (see Table 1). As changes in the microbiological status of a patient were barely included in the reports from the rehabilitation sites, we could not assess this outcome. Although we believe that it is the responsibility of the rehabilitation site to demonstrate lack of transmission, we have recently started to also closely monitor our patients before and after rehabilitation, but in the future evaluation of respiratory pathogens by clonality is required to really assess the cross-infection risk. In the so called summer camps, where patients were encouraged to have close psychosocial contacts and where no structural measures for hygiene were implemented or controlled [3-6], but also in rehabilitation programs when the appropriate measures were not undertaken to prevent clonal spread of cystic fibrosis bacteria [19, 20], person to person transmission of bacteria have been demonstrated. Therefore unequivocally the rehabilitation sites have to demonstrate that they are safe from a hygiene aspect. Small cohorts have suggested if the appropriate hygienic precautions are introduced, transmission can be prevented [9, 21]. In particular, lack of transmission has recently been demonstrated for older cohorts at the Israel site [9].

In patients with many severe chronic pulmonary diseases other than cystic fibrosis, rehabilitation programs in the Western world have successfully improved key outcome variables including lung function, exercise performance and health-related quality of life [1]. From our study and in agreement with other studies mentioned, we can conclude that such goals might also be achieved for patients with cystic fibrosis. If the rehabilitation programs are run for patients with cystic fibrosis at a maximum level of hygienic precautions to prevent cross-infections [22], together with individual improvements of health, the overall health care costs might be reduced. However, it is necessary in the short term, to improve the quality of the reports received from the rehabilitation sites and to receive non-biased and standardized assessments of acknowledged outcomes from all subjects. This will help to identify patients who do not profit from the program and target efforts to specifically address their needs. In the long term and with the correct designs implemented it will either be possible to demonstrate safety and efficacy of the programs, or to conclude that this goal cannot be achieved by current programs which must then be stopped and replaced by improved rehabilitation efforts for cystic fibrosis patients. All this is the principal responsibility of the rehabilitation sites. On the one hand the support coming from the insurance companies who pay for the programs is appreciated; on the other hand, these companies should be encouraged to help to further improve the standards to be set for a successful rehabilitation.