Individuals and families affected by Cystic Fibrosis (CF) know that exacerbations are not just stressful, but also dangerous. CF exacerbations are associated with lung function decline, poor quality of life, and the increased risk of death or need of a lung transplant. Preventing and treating these exacerbations are important factors in giving CF patients the healthcare that they need. Currently, guidelines for the treatment of CF exacerbations rely only on expert opinion since there is not enough information from clinical trials to make standard recommendations. A recent article published by The Journal of Cystic Fibrosis reviews three articles that summarize the results of the first Standardized Treatments of Pulmonary Exacerbations (STOP) study. The STOP study was designed to provide a baseline for future studies looking at improving the outcomes of CF exacerbations. This was an observational study that was done at 11 CF centers in the United States.
A review of articles
The first article that was published about the STOP study looked at 220 patients who were hospitalized for CF exacerbations. The majority of these patients were adults and were often infected with P. aeruginosa (the major pathogen in the lungs of CF patients). These patients with exacerbations had moderate to severe lung function impairments, and about 43 percent had been treated with IV antibiotics in the six months before their current exacerbation. When recruited patients typically had been experiencing symptoms for 7 to 21 days. Their symptoms were analyzed by using a patient reports of symptomology and outcomes. The results showed that among the patients studied, forced expiratory volume (FEV) varied between showing a decrease, and being the best FEV that the patient had seen in 6 months.
The second article that was examined looked at what treatment practices healthcare providers used, and what the outcomes of the patients were within 28 days, and again at 6 months after IV antibiotic initiation. The study revealed that both the IV and oral antibiotics that providers choose tend to vary drastically. On average IV antibiotic treatment lasted for 14 days. Overall, results showed that the treatments chosen proved to be somewhat effective for the group as a whole. Symptom reduction was noted and FEV increased on average by 9 percent. At six months, FEV was fully recovered by only 39 percent of the exacerbations. Additionally, 35 percent of patients did not even recover 90 percent of their best 6-month FEV.
The study showed that there is significant variability in the treatment goals and expectations of providers when they are caring for patients with exacerbations. Additionally, the study revealed that when providers are assessing patients, their subjective impressions do not line up well with actual clinical outcomes. Of the providers caring for patients with exacerbations, they felt that their treatment methods were sufficient in treating 84 percent of exacerbations, when in fact, clinical improvement was modest at best.
In the third article that the Journal of Cystic Fibrosis reviewed looked at outcomes and scenarios for designing interventional studies using the results that were observed in the STOP study. The authors of the third article decided that using a combination of the mean change in the Chronic Respiratory Infection Symptom Score (CRISS) questionnaire (the questionnaire that patients use to self-report symptoms) and the mean change in FEV since treatment initiation, would be the most sensitive measurement tool.
The results of the STOP study showed that patients who are experiencing exacerbations may receive antibiotics based on a wide variety of symptoms. There is no current standardized starting point when managing these exacerbations. By looking at the variability in the type of care that patients can receive, hopefully providers will be able to use objective evidence to develop standard recommendations for care. Hopefully these results will also show the CF healthcare community that perhaps providers should rely a bit more on hard evidence and facts rather than whether or not they “feel” that a patient has recovered successfully. While a key component of providing healthcare is trusting one’s instinct and experience, research exists for a reason, and the research is saying that CF exacerbation management is not as successful as most providers think it is.
STOP study limitations
As with any study it is important to review its limitations so that we do not place undue confidence in its results. With research studies, sample size is important. The STOP study sample size was relatively small. They only used a small number of United States CF centers and limited the study to patients who were expected to stay hospitalized for at least 5 days. This means that the study is limited in the sense that we cannot say if the results are applicable to patients who have not been admitted to the hospital. Additionally, the CRISS questionnaire that has been used to look at patient symptoms is available in many languages, but its applicability to other countries has not been examined. This further limits the population to which the study results are applicable to. Finally, there is still more knowledge that researchers and healthcare providers alike need to gather on causes of CF exacerbations. Things such as viral infections, bacterial infections, and environmental factors can all play a role in sparking a CF exacerbation. Without being able to differentiate between causes, determining appropriate interventions can be extra challenging.
The last limitation of the study is that there are not many reliable biomarkers that can be used to confirm the diagnosis of, or determine where an exacerbation originated. Having a biomarker to use to confirm the presence and type of exacerbation could allow for smaller sample sizes in future studies due to increased patient specificity.
Overall the STOP study and the review of the three articles in the Journal of Cystic Fibrosis has increased our knowledge about where the gaps are in caring for patients with CF exacerbations, and where the gaps are in conducting research about CF exacerbations. There is now clearly a need for treatment guidelines that are based on clinical evidence to be developed. This will ideally help decrease the variability in the treatment options that patients receive while also increasing clinical outcomes. Additionally, development of criteria for what is considered “successful” or “unsuccessful” treatment of a CF exacerbation will help ensure that patients are all receiving equal access to the care that they deserve. The studies within the STOP study have also confirmed something that we have known for a while. That CF exacerbations can greatly impact the life of the patient. These events can lead to loss of lung function in patients who undergo current exacerbation treatment. The first STOP study is being followed up with a STOP II study that will look more closely at the efficacy and safety of durations of IV antibiotic treatment in patients in the hospital or at home. This study has also showed us that more research is needed to look at what antibiotics are the best first-line treatment option for patients with a CF exacerbation, as well as what additional medications should be used to manage the situation.