Clinical Manifestations

Gastrointestinal symptoms

Around 85–90% of patients with cystic fibrosis have exocrine pancreatic insufficiency. Typical signs are greasy stools, flatulence and poor weight gain. It causes maldigestion and malabsorption of nutrients, along with steatorrhoea, fat-soluble-vitamin deficiency and malnutrition. Low faecal elastase is an excellent indicator of pancreatic insufficiency [Gelfond and Borowitz, 2013]. Seventy years ago, when the disease was first described, children died because of malnutrition. Since pancreatic replacement enzyme therapy became available in the 1950s, cystic fibrosis prognosis has changed significantly.

Around 15% of infants with cystic fibrosis are born with meconium ileus and distal intestinal obstruction syndrome may occur in patients of all ages, due to partial or complete bowel obstruction by more voluminous and viscous faeces. Medical, rather than surgical, management is recommended [Gelfond and Borowitz, 2013]. Patients may develop focal biliary cirrhosis due to obstruction of intrahepatic bile ducts [Wilschanski and Durie, 2007]. Portal hypertension and oesophageal varices can develop secondary to the cirrhosis.

Other gastrointestinal manifestations are: acute pancreatitis, gallstones, cholangiectasis, gastroesophageal reflux, rectal prolapse and cancers of the digestive tract [Kelly and Buxbaum, 2015].

Pulmonary disease

Cystic fibrosis lung disease is characterised by chronic airway infection and inflammation leading to bronchiectasis. Lung disease starts early in life as demonstrated by bronchoalveolar lavages showing frequent bacterial infection and neutrophilic inflammation in asymptomatic infants diagnosed by newborn screening [Sly et al., 2009; Pillarisetti et al., 2011]. Moreover, chest computed tomography showed evidence of bronchiectasis in about a third of patients within the first few months of life [Stick et al., 2009]. Classically, airways are first colonised with Haemophilus influenzae, then Staphylococcus aureus and finally Pseudomonas aeruginosa – which is associated with a worse prognosis [Emerson et al., 2002]. Other pathogens such as Gram-negative bacterial species, non-tuberculous mycobacteria or Aspergillus spp. may also be present. Symptoms of cough and sputum production are common. Exacerbations of pulmonary disease occur periodically, and are treated by antibiotics in order to restore lung function. Lung disease and progressive airway obstruction are monitored via the maximum forced expiratory volume over 1 second (FEV1), which will typically show a gradual decline over years. Pulmonary exacerbations are associated with a more rapid loss of lung function and a worse prognosis [Sanders et al., 2011]. The progression of airway disease leads to eventual respiratory failure which is the main cause of death.

New microbiological techniques based on molecular analysis and so-called ‘next generation sequencing’ have identified a large range of bacteria in the airways of normal subjects and in patients with cystic fibrosis. It is not yet clear if some of the bacteria of this microbiota are pathogenic and should be treated. The lung microbiota in cystic fibrosis includes anaerobic bacteria, particularly Prevotella species [Tunney et al., 2008]. Some studies have suggested that bacterial community diversity is associated with a mild lung disease phenotype [Zhao et al., 2012].

Patients may also suffer from acute respiratory complications that require intervention, including pneumothorax and massive haemoptysis [Flume, 2009]. Allergic bronchopulmonary aspergillosis is also seen in patients with cystic fibrosis.