Falling through the Cracks—The Impact of Care Gaps on Lung Function Loss in Cystic Fibrosis

The cystic fibrosis (CF) care model, built on a foundation of quarterly clinic visits and comprehensive team-based care, has been credited for the remarkable advances in CF outcomes and longevity over the past several decades. Aggressive and timely monitoring of lung function to diagnose pulmonary exacerbations, sputum microbiology to detect the growth of new pathogens, weight to ensure adequate nutritional status, and adherence to therapies critical to maintaining health have formed the pillars of CF care since the first multidisciplinary CF clinic was established in the 1950s (1). Evidence in support of this care model is limited, but CF centers that have the highest visit frequencies have, on average, the highest center-based lung functions, which suggests that close patient monitoring improves respiratory outcomes (2, 3). Consequently, missed clinic visits would be expected to result in worse health outcomes.

In this issue of AnnalsATS, Sears and colleagues (pp. 1250–1257) utilized U.S. Cystic Fibrosis Foundation Patient Registry (CFFPR) data from 2004 to 2016 to investigate the relationship between missed clinic visits and lung function changes over time in people with CF (pwCF) (4). Using a threshold of at least 12 months of missing CFFPR data to define discontinuous care, they found that these patients had a modest but significantly lower lung function at their subsequent visit compared with those with continuous care. As hypothesized, this difference was amplified in young adults, and especially in young adults with F508del homozygous cystic fibrosis transmembrane conductance regulator (CFTR) genotypes. Notably, the rates of discontinuous care were high, with 35% of patients having at least one episode of discontinuous care lasting 12 months or longer over the study period, and higher rates of discontinuous care were observed in older pwCF.

This study has many strengths. First, the use of data from the CFFPR over a long study period permitted the analysis of a very large (more than 24,000 individuals and 1 million clinical encounters) and complete dataset. Important covariates were also considered as to their potential confounding effect on lung function decline, as established in previous studies. The cohort included were ages 6–45 years, which was enriched for pwCF who are more likely to be vulnerable to lung function loss, as older patients tend to have milder lung disease (because of less severe genotypes) with lower rates of lung function decline (5).

An important finding from this study is that the largest lung function decline was observed in the adolescent and young adult cohort with discontinuous care. This is consistent with prior research demonstrating that lung function decline accelerates as pwCF transition from adolescence to young adulthood (6). This can be a vulnerable time where individuals are establishing independence, forging relationships, and discovering their identities. In patients with chronic illness, this may be associated with inattention to self-care, poor adherence to chronic maintenance therapies, and lower attendance to routine medical visits. It is during this same period when pwCF are transitioning their care from pediatric to adult CF centers. Sawicki and colleagues previously reported that 13% of transitioning CF patients had at least a 365-day gap during this transfer and, notably, these prolonged gaps were more likely to occur in pwCF who were younger than 18 years old, suggesting that delays in transitioning might be beneficial in some cases (7).

The study period analyzed (2004–2016) predated the widespread availability of highly effective CFTR modulator therapy (HEMT), particularly before elexacaftor/tezacaftor/ivacaftor (brand name: Trikafta) was approved in 2019. Although ivacaftor (brand name: Kalydeco) was available in 2012 for patients with select gating mutations, and lumacaftor/ivacaftor (brand name: Orkambi) was available in 2015 for patients homozygous for F508del, CFTR modulator use was not captured in their datasets. HEMT can change the trajectory of CF pulmonary disease and significantly attenuate the rate of lung function decline; therefore, it may mitigate the impact of gaps in care on lung function decline (8, 9). The interaction between HEMT use and care continuity as they contribute to rate of lung function decline will be important to study in the current era of CF management.

For the discontinuous-care group, lung function decline was less significant in patients with milder genotypes, highlighting how the frequency of follow-up may need to be individualized on the basis of disease severity, trajectory, clinical characteristics, and comorbidities. Older patients in the study had more frequent rates of discontinuous care; however, this was not associated with increased lung function decline. There is a need for further research in this area, as our aging CF population may have different follow-up requirements with the development of new comorbidities and complex care needs. It is possible that future guideline-based standards of care may involve less frequent clinic visits in the age of disease-modifying HEMT in CF.

On a final note, the study was not able to evaluate the role of medication nonadherence as an important mediator in the relationship between discontinuous care and lung function decline. In addition to CFTR modulators, pwCF often rely on CF centers for refills of other chronic maintenance therapies such as mucolytics, chronic suppressive antibiotics, and other inhaled medications. In some cases, they are even required to pick up their medications from hospital-based pharmacies in conjunction with clinic visits. Many of these other medications have been shown to reduce the risk of pulmonary exacerbations and increase lung function in pwCF (10).

This article nicely highlights how integral continuity of care is in optimizing health outcomes in CF. The evolution of technology, expedited by the coronavirus disease (COVID-19) pandemic, has allowed us new opportunities for remote health monitoring and virtual health assessments that can be incorporated into routine care to reduce gaps in care for pwCF who live far from CF clinics and would otherwise be lost to follow-up. With the advent of disease-modifying HEMT among other therapies for rarer genotypes on the horizon, we are clearly in a new era of CF care, and our approach to routine follow-up may need to evolve as well. Last, we must consider that individuals who may be the most vulnerable to gaps in care in the future will include pwCF who are not eligible for HEMT. These individuals tend to be in ethnic-minority groups who may also lack access to technologies required to participate in virtual health assessments with the potential to further exacerbate health inequities.