Discussion
This study demonstrates that most patients with normal pulmonary function, measured by FEV1, already have significant lung disease according to physiological (measured by LCI), structural (HRCT changes) and clinical (chronic PA and PEx) parameters. Furthermore, having high LCI and/or high CT scores was associated with chronic PA infection, increased number of major PEx and more days of IV antibiotic trreatment, all indicators of CF disease activity and predictors of subsequent FEV1 decline.
It was shown in infants, diagnosed through newborn screening, that early pulmonary abnormalities can be identified already in the first years of life18. Furthermore, it has been shown previously that high LCI levels can be found in asymptomatic infants or small children19-23. In this study, different from most of the published studies, the majority of patients were teenagers and adults, and as it is known, in older patients FEV1 is considered to best represent disease severity5.
FEV1 in the normal range may be interpreted as ”normal lungs”, which may lead to an erroneous misinterpretation of the severity of the disease, and can result in fewer treatments offered by the CF team, or decreased adherence to treatments by the patients. However, as shown in the current study, FEV1 in the normal range, is not sensitive enough to identify early and even significant lung disease and therefore, it is important to follow specially patients with normal or slightly decreased FEV1 regularly using other clinical parameters. Frequent monitoring of lung disease by LCI and chest CT, repeated sputum cultures with immediate eradication of newly acquired bacterial infections, and early treatment of PEx may prevent or at least postpone irreversible lung damage and disease progression.
Frequent monitoring of CF patients using chest CT scans does carry a potential risk due to radiation exposure and is therefore not always performed routinely. The new imaging technology with short duration of radiation exposure and the low radiation CF protocols are associated with minimal radiation. Furthermore, studies demonstrated that acute structural changes can be reversible when treated immediately24-30. The very strong correlation between LCI and Brody Score suggests that LCI can be used more frequently and as long as LCI levels remain normal, routine chest CT scans can be postponed to the time when levels of LCI become abnormal or deteriorate. It has been shown that in young children, inhalations with hypertonic saline24 and treatment of pulmonary exacerbations25 can improve LCI. Furthermore, CFTR modulator therapy was also shown to improve LCI levels26, suggesting the interventions at this stage of lung disease can reverse abnormalities.
An important result of this study is the correlation between the clinical parameters of CF severity such as PA infection, PEx and days of IV antibiotic treatment with abnormal LCI and TBS values. Therefore, it is essential to early identify and treat all changes with the aim to prevent or reverse disease progression.
In conclusion, the importance of this study lays in the demonstration that regardless of their age, most CF patients with normal FEV1 already have evidence of lung disease, as detected by LCI and chest CT scan, and is associated with increased PEx and more days of IV treatment. Additional studies are necessary to determine if early and aggressive treatments will preserve or reverse changes detected by LCI and CT scans and if early treatment with the current and future CFTR modulators will avoid or postpone early lung damage.