Bicarbonate and acid-base balance in cystic fibrosis

Background: Metabolic alkalosis is common in people with Cystic Fibrosis (CF), and is often presumed to be the result of Pseudo-Bartter’s syndrome (PBS). However, clinical experience suggests that both metabolic alkalosis and hyperbicarbonataemia occur, relatively frequently, in the absence of PBS. The clinical significance and aetiology of these phenomena remain poorly understood. Aims: The main goals of this thesis were: (1) to characterise the level of serum bicarbonate concentration in clinically stable people with CF and see how commonly it was elevated; (2) to assess the clinically significance of elevated bicarbonate; and (3) to evaluate if acid-base balance was differently altered in CF compared to other respiratory conditions. In addition, this thesis aimed at (4) examining the cause of hyperbicarbonataemia, and (5) to ascertain if respiratory support techniques could normalise bicarbonate levels and gas exchanges in people with CF. Findings: (1) Serum bicarbonate levels were elevated in stable individuals with CF. Comorbidities, age, and sex were independently associated with hyperbicarbonataemia. (2) In patients with CF, bicarbonate increases significantly in the year prior to death. (3) Metabolic alkalosis occurred frequently in CF, in both the clinically stable and during pulmonary exacerbations. Acute and chronic hypercapnic respiratory failure were the most common acid-base disturbances seen prior to death. (4) Urinary bicarbonate excretion did not increase in patients with CF, despite the hyperbicarbonataemia. (5) Individuals, with isolated raised serum bicarbonate, responded to hypoxic stimulus in a similar way to patients with daytime hypercapnia. (6) Transient hypoventilation during exercise was observed in people with CF and severe lung disease. (7) Nasal high-flow therapy reduced CO2 during exercise. (8) Non-invasive ventilation stabilised serum bicarbonate levels in individuals with CF. Conclusion: Raised bicarbonate appears to be a marker of disease severity in CF, and has the potential of being an useful prognostic biomarker, especially in the last few years of life. Metabolic alkalosis and respiratory acidosis are the most common acid-base disturbances seen, with hyperbicarbonataemia being likely the result of a combination of transient hypoventilation, hypercapnia and the kidney’s inability to increase urinary excretion due to defective CFTR. Respiratory support techniques are likely to control the ventilatory component of hyperbicarbonataemia by improving gas exchanges, while the new CFTR modulators may normalise renal bicarbonate exchange