Dr Kate Gonski ( left ) Paediatric respiratory and sleep physician , Sydney Children ’ s Hospital Network , Randwick , NSW .

Dr Anna Middleton ( right ) Senior cystic fibrosis physiotherapist , Sydney Children ’ s Hospital Network , Westmead , NSW .

Carla Rowe ( left ) Senior cystic fibrosis dietitian , Sydney Children ’ s Hospital Network , Westmead , NSW .

Dr Bernadette Prentice ( right ) Paediatric respiratory physician and director of cystic fibrosis services , Sydney Children ’ s Hospital Network , Randwick , NSW .

Copyright © 2023 Australian Doctor All rights reserved . No part of this publication may be reproduced , distributed or transmitted in any form or by any means without the prior written permission of the publisher . For permission requests , email : howtotreat @ adg . com . au

This information was correct at the time of publication : 16 June 2023

BACKGROUND

CYSTIC FIBROSIS is an autosomal

recessive monogenic genetic condition that primarily affects the lungs and the gastrointestinal ( including pancreas and liver ) and reproductive systems . It is the most common life-limiting genetic disorder in Australia , and there is currently no cure . 1

With early diagnosis through the newborn screen ( NBS ) and improvements in treatments , progression of the disease can be significantly slowed . 2 The Australian Cystic Fibrosis Data Registry has shown rapid improvements in life expectancy for Australians born with cystic fibrosis ( CF ); there is an expectation that this will continue to improve because of the recent availability of genetic modulation therapies through the PBS . 3

Patient engagement with a GP is particularly important to provide continuity of care at all life stages , encourage adherence and address health concerns not specific to CF . This How to Treat covers CF from diagnosis to specialist referral and includes new therapies that are improving life expectancy . It aims to ensure that GPs are aware of carrier genetic screening , potential clinical presentations , referral pathways and common and novel treatments being used in CF management .

AETIOLOGY AND PATHOPHYSIOLOGY

CF has traditionally been the most

common life-limiting disease in the Caucasian population worldwide . 4 Clinical manifestations of CF are caused by a defect in the CF transmembrane conductance regulator ( CFTR ) protein : a chloride channel widely distributed throughout the body ( see figure 1 ). CFTR is an essential regulator of many mucosal surfaces ’ fluid and electrolyte homeostasis . 1 Dysfunction or absence of the CFTR results in accumulation of viscous mucus and ultimately leads to inflammation , recurrent infection , malnutrition and progressive multi – organ dysfunction . 1

More than 2000 CFTR mutations have been documented , resulting in a spectrum of disease phenotypes and severity . 5 At present , the functional consequences of all the variants have not been defined . 6 Where the functional consequences are known , variants can be divided into seven different classes based on CFTR function . 7 , 8 Classes I-III and VII are associated with little or no CFTR function and therefore suggest a severe phenotype , whereas classes IV-VI have some CFTR function — termed residual function mutations — and these tend to be less severe . 6 Figure 2 describes the mechanism for each

class . There is , however , significant variation because of non-CFTR genetics and environmental factors . 1

The most common gene variant is F508del , with 90 % of CF patients in Australia being either heterozygous or homozygous . 9 This is followed by G551D , with 4 % of the CF population carrying this variant . 9

EPIDEMIOLOGY

EPIDEMIOLOGICAL changes have occurred in both incidence and survival ( significantly increased in recent decades ). 4 The worldwide incidence of CF has been estimated between one in 3000 and one in 6000 live births . 11 The incidence detected in Australia through NBS is one in 3000 . 9 The incidence is decreasing in most countries where genetic-based health policies allow prevention through prenatal screening and preimplantation diagnosis . 12

While CF remains a serious disorder , recent changes in treatment and management have changed the characteristics of the CF population . What was previously an exclusively paediatric disease is now becoming a disease of the adult , where there are additional pathologies to manage . 12

CF occurs in males and females ; however , it is more prevalent in males . In Australia , 52.8 % of patients with CF are male . 9 It is currently unclear why

there is a sex disparity in CF survival , but studies performed over the past several decades have suggested that sex hormones might contribute to poor pulmonary outcomes in females . 12

CLINICAL FEATURES

DYSFUNCTION in the transport of

chloride ( and other ions ) leads to the generation of thick , viscous secretions in the lungs , pancreas , liver , intestine and reproductive tract , and increased salt content in the sweat gland secretions . 13 Progressive lung disease is the major cause of complications and patient mortality . 6 The course of the disease can vary , and complications may be evident at birth or decades later , with some expressing mild or atypical symptoms . 13 Consider a diagnosis of CF even if the patient only exhibits a few typical signs and symptoms . Table 1 lists the clinical manifestations of CF ( see figures 3 and 4 ).

Respiratory exacerbations

Transient airway infection with pathogenic

bacteria tends to occur early in life . Patients with CF are commonly infected with Staphylococcus aureus or Pseudomonas aeruginosa . Chronic airway infection leads to chronic inflammation and , ultimately , radiographic evidence of bronchiectasis , which may be irreversible . Other