Comorbidities

Cystic fibrosis-related diabetes

Cystic fibrosis-related diabetes (CFRD) is one of the most common comorbidities of cystic fibrosis, with a prevalence of 1–2% in children, 15–19% in adolescents, and 40–50% of adults with cystic fibrosis [Moran et al., 2009; Ode and Moran 2013]. Although cystic fibrosis-related diabetes has features in common with type 1 and type 2 diabetes, it has a separate pathophysiology. Insulin deficiency is mainly due to destruction of endocrine ß-cells from pancreatic tissue damage due to abnormal CFTR function. Cystic fibrosis-related diabetes is associated with a more rapid decline in lung function and worse nutritional status, both factors leading to increased morbidity and mortality [Ode and Moran 2013]. Annual screening for CFRD is recommended from age 10 in all patients with cystic fibrosis. Testing blood glucose 2 hours after a glucose load is the most sensitive test at present [Moran et al., 2010; Waugh et al., 2012]. However, novel diagnostic methods are currently under evaluation [Prentice et al. 2016].

Cystic fibrosis-related bone disease

Cystic fibrosis-related bone disease (CFBD) is an increasingly recognised complication. Osteopenia, osteoporosis and frequent fractures have been reported in many studies. In older patients with cystic fibrosis, bone disease is associated with severe lung disease, poor nutrition, specific CFTR genotypes and physical inactivity. Screening for metabolic bone disease is recommended for all adults with cystic fibrosis [Stalvey and Clines 2013]. Arthropathies are also quite common in patients with cystic fibrosis.

Infertility

The vast majority of adult males with cystic fibrosis (around 99%) are infertile due to congenital bilateral absence of vas deferens (CBAVD) [Jarzabek et al., 2004; Ahmad et al., 2013]. Puberty is delayed, but testicles are normal and spermatogenesis still occurs. Although females with cystic fibrosis generally have anatomically normal reproductive tracts, fertility is reduced, with malnutrition being associated with delayed puberty and amenorrhoea [Jarzabek et al., 2004; Ahmad et al., 2013]. Nearly 50% of females with cystic fibrosis may be able to conceive spontaneously [Ahmad et al., 2013].

Drug adverse effects

Allergic reactions to medication are frequent, and may make it difficult to prescribe effective antibiotic treatment for pulmonary exacerbations. Aminoglycosides in particular may induce kidney injury and otovestibular toxicity. Cumulative exposure will increase these risks [Plant et al., 2013].

Kidney disease

Chronic kidney disease is rare in patients with cystic fibrosis [Quon et al., 2011], but its prevalence increases with age [Schechter and Stecenko, 2011]. Risk factors for chronic kidney disease include cystic fibrosis-related diabetes and treatment toxicity (from aminoglycosides or treatment for lung transplantation) [Plant et al., 2013].

Other

Chronic rhinitis, sinusitis and nasal polyps are common [Rozsasi and Keck, 2003]. Patients also exhibit increased susceptibility to dehydration during periods of sustained high ambient temperatures [Fustik et al., 2002].

Cystic fibrosis-like phenotypes

A CFTR-related disorder is defined as a clinical entity associated with CFTR dysfunction that does not fulfil the diagnostic criteria for cystic fibrosis [Bombieri et al., 2011]. CFTR-related disorder describes individuals with a cystic fibrosis phenotype in at least one organ system, such as congenital bilateral absence of vas deferens (CBAVD), acute recurrent or chronic pancreatitis, diffuse bronchiectasis or chronic sinusitis, and biochemical or genetic evidence of CFTR dysfunction [Bombieri et al., 2011]. Evidence of CFTR dysfunction may constitute:

  • an intermediate sweat test
  • identification of CFTR mutations with unclear pathogenetic role
  • another test showing abnormal CFTR function such as the nasal transepithelial potential difference or the intestinal current measurement.

See the diagnosis section for further information.