Cystic Fibrosis Not an Easy Diagnosis

Abstract

Abstract: Introduction: The NBS program facilitate early diagnosis of cystic fibrosis (CF) patients, which resulted in reduced mortality rate and improved clinical outcome. However, it introduced new group of patients who screened positive through NBS but have less than two CF-causing gene mutation or normal sweat chloride test (SCT). This group of patients defined as Cystic Fibrosis Screened Positive Inconclusive Diagnosis (CFSPID) during an expert consensus in 2015. However, the knowledge of the clinical outcome of the CFSPID is limited. Also. the clinical management and follow-up of these patients is variable between centers. Aim: 1) To describe the current CFSPID/CRMS population at the Royal Brompton hospital (RBHT), and to contribute to the knowledge of this patients’ group. 2) To identify well children who met the CFSPID/CRMS criteria, but was born before the CFSPID/CRMS era or before the new guidelines and initially followed at CF clinics. Methods: This is an audit of the CFSPID/CRMS population at RBHT. All Patients met the CFSPID/CRMS criteria were included. Also, the patients who would have met CFSPID/CRMS criteria, but were born before the CFSPID/CRMS era or before the new guidelines were introduced, was also included in the audit. Medical records for all patients were reviewed for genotypes, SCT, IRT, positive airway cultures, prophylactic and IV antibiotics, physiotherapy, FEV1, and elastase level. Results: Total population was 27 patients; 13 patients were initially followed as CFSPID/CRMS in a general respiratory clinic, while 14 patients were initially followed as CF. All the study population was pancreatic sufficient. The predominant genotype was the heterozygous (F508del/R117H-7T). All the CFSPID/CRMS group was screened through the NBS programme, however, two patients were not screened positive initially and labelled later due to other reasons; one due to the diagnosis of older sibling with CFSPID/CRMS, while the other experienced symptoms and the genetic testing was conducted because both parents were known to be CF carriers during an IVF process. All the CFSPID/CRMS group remain well. However, three patients were subsequently moved into the CF clinic; one due to increased symptoms, the other two were twins: twin-1 was moved due to increased symptoms and repeated positive airway cultures including pseudomonas species with evidence of tracheomalacia by bronchoscopy, while twin-2 was moved with his twin due to practical reasons even he was asymptomatic. However, none of these patients had increasing SCT. In the CF group, 4 patients were born before the NBS era, while the other 10 patients were screened positive through NBS, but were born before the CFSPID/CRMS era or before the new CFSPID/CRMS guidelines. All patients in the CF group had symptoms and positive airway cultures and were prescribed physiotherapy and some was on respiratory treatment and prophylactic antibiotics. However, all patients maintained normal pulmonary function test. Two patients were subsequently moved into the CFSPID/CRMS group; one due to mild clinical course while the other moved after evidence of normal chloride movement by NPD. One patient had subsequent SCT >60 mmol/L which was confirming of CF. Conclusion: The CFSPID/CRMS group remain well in general, but some patients may progress into CF. However, it is essential not to overlook other contributing factors that can increase symptoms in children such as gastroesophageal reflux and pre-school wheezes syndrome. Therefore, patients should be evaluated for the CFSPID/CRMS label in isolation of other contributing factors. There was no reliable predictor for clinical outcome. The patients followed in the CF clinics had more symptoms, positive cultures, and treatment prescriptions. However, this group was extremely older and manged according to the aggressive protocol-driven CF