E. De Wachter

Characteristics of gastroesophageal reflux and potential risk of gastric content aspiration in children with cystic fibrosis.

Objectives: Increased gastroesophageal reflux (GER) is common in children with cystic fibrosis (CF). We studied the occurrence of acid, weakly acidic (WA), and weakly alkaline (WALK) reflux in children with CF and evaluated a possible surrogate marker for risk of gastric content aspiration. Patients and Methods: Twenty-four children with CF underwent impedance-pH monitoring for detection of acid (pH < 4), WA (pH 4-7), and WALK-GER (pH ≥ 7). In 11 children, cough was objectively recorded with esophageal manometry and the symptom association probability was calculated to determine the reflux-cough relation. Presence of bile acids (BA) was measured in the saliva of 65 patients with CF and 23 healthy children, respectively. Results: Sixteen of the 24 children had increased GER (esophageal acid exposure). The majority of reflux events were acidic in nature. WA reflux was less common and WALK reflux was rare. The sequence reflux-cough was found in 8 of the 11 children and 1 of 11 children had a positive symptom association probability for reflux-cough. The sequence cough-reflux was found in only 3 of the 11 children. Only a small fraction of the total esophageal acid and volume exposure was secondary to cough. Twenty-three of the 65 children with CF had BA in saliva compared with none of the healthy controls. Conclusions: Although WA-GER is uncommon, acid GER is prevalent in children with CF. It is a primary phenomenon and is not secondary to cough. One third of the children with CF have BA in saliva, which may indicate an increased risk for aspiration. However, the impact of salivary BA and potential aspiration on CF pulmonary disease needs further investigation.

The relationship between gastroesophageal reflux and cough in children with chronic unexplained cough using combined impedance–pH–manometry recordings

Assessment of the reflux–cough association in children is challenging. Esophageal (impedance) pH recording is sensitive to recognize reflux. However, cough recorded by an event marker, possibly lacks accuracy. We aimed to study the exact time relationship between reflux and cough in children with chronic cough.

A semi-blinded study comparing 2 methods of measuring nasal potential difference: Subcutaneous needle versus dermal abrasion

BACKGROUND According to European and US protocols, two nasal potential difference (NPD) measurement methods are considered acceptable, although they have not been formally compared: subcutaneous agar-filled needle with calomel (Ndl) and dermal abrasion with conducting cream and Ag/AgCl electrodes (Abr). We compared both in CF and healthy volunteers (HV), assessing their discriminative value and subjects preference. METHODS Twelve classic CF and 17 HV underwent both NPD methods, performed by one operator in random order. A written questionnaire, assessing preference, was completed after each test. Tracings were coded, scored in a semi-blinded fashion and categorised as CF/non-CF. RESULTS 110 tracings (56 Ndl/54 Abr) were collected: 42/110 scored CF and 68/110 non-CF, showing a good correlation. No significant preference for either method was reported. CONCLUSION Both NPD methods are similar in terms of discriminative value and subjects preference, comparing classical CF and HV. For diagnosing CF, the operators preferred NPD-method may be used.

ePS06.5 Burkholderia cepacia complex acquisition: A threat in all CF patients?

Introduction Acquisition of Burkholderia cepacia complex (Bcc) bacteria is considered to be associated with worsening of CF lung disease. Moreover, because of its resistance to antibiotics, Bcc is considered a threat in CF. Method Data from the Belgian CF Registry (year 2000–2010) were obtained. Inclusion: Bcc-infected patients with entries on lung function, BMI and days of IV treatment in at least 3 y after Bcc acquisition. For each case, we included 2 controls, matched for age at index year (year of first Bcc infection), pancreatic status, sex. FEV 1 , days of IV antibiotics and hospitalization were used as surrogates for disease burden. Cumulative data up to 2 y before index year were compared to values after infection using Rank sum test. Rate of decline in lung function was adjusted for baseline lung function, age, sex. Results Prevalence of Bcc in CF is low in Belgium ( B. multivorans. FEV1 at index year had lower tendency in the cases, however without significance. The number of days of IV treatment had higher tendency in the cases (p = ns). FEV1 decline after Bcc acquisition was comparable in cases and controls (–1.1%, SD = 0.5, vs –0.99%, SD = 0.4, p = 0.24). BMI slopes were also comparable between groups. Conclusion Our study suggests that Bcc infected patients are in no worse clinical condition and demonstrate no faster clinical deterioration compared to Bcc-uninfected patients. However, registry data are collected retrospectively and bear a risk of inaccuracy. Therefore, these results should be confirmed in a prospective, longitudinal study.

339 Increased proportion of CF patients with normal FEV1 over an 11-years nation-wide study: have patient characteristics changed?

Objectives: From April 2012, UK centres will be funded based on treatment patients needed the 12 months leading up to annual review the previous calendar year. Thus, funding will be based on data 3−15 months old, potentially underestimating patients’ health needs. We investigated whether data from the previous calendar year (only 3 months old) were better at predicting subsequent treatment needs. Methods: The following data were collected retrospectively from all patients treated at our centre from 2008 to 2011: number of in-patient days (IP days), number of days of iv antibiotics (IV days), and month of annual review. Wilcoxon matchedpairs signed-rank and Kolgorov–Smirnov tests were used to test whether data from the previous calendar year were better than annual review data from that year at predicting treatment needs the following calendar year. Results: 103 patient-years (41 patients) were analyzed. IP days differed by a mean 2.9 days (range −66 to +132) from the previous calendar year, compared to a mean 3.5 days (range −100 to +144) from annual review. IV days differed by a mean 3.2 days (range −97 to +178) compared to a mean 5.1 days (range −78 to +218). Differences in the means were not significant (p = 0.33, Wilcoxon). When data were analyzed to look at the variation in treatment band there was no significant difference. Conclusion: Though treatment needs for some individuals changed dramatically from year to year, overall the treatment needs of patients in a given calendar year were reasonably predicted by the treatment given as measured at patients’ previous annual reviews. There would be no benefit in using calendar year data rather than annual review data.

ePS04.3 CF patients' pain experience with different sampling methods for bacterial culture

fumigatus were not found in these swabs taken in 2015. 7/26 patients had no critical bacterial results on both quality controls. 2/26 patients had critical bacteria in both quality checks. 2/26 patients had critical bacteria in 2015 despite the nebulizer were not contaminated in 2013 (Aspergillus fumigatus and Staphylococcus aureus, Alcaligenes faecalis). Conclusion: The implementation of this new simplified hygiene recommendation seems efficient on nebulizer contamination.

67 CF patients with a declining FEV1: At risk for acquisition of Burkholderia cepacia complex infection?

Introduction Burkholderia cepacia complex (Bcc) infection is considered to be associated with worsening of CF lung disease. Patient to patient spread has been reported, however mechanisms of acquisition of Bcc are not well understood. Method: Data from the Belgian CF Registry (year 2000–2010) were collected. Inclusions: Bcc infected patients with entries on lung function in at least 1 y before and 3 y after Bcc acquisition. For each case, we included 2 controls, matched for age at the index year (year of first Bcc infection), pancreatic status, sex. Cumulative data up to 2 years before index year were compared to values obtained after infection using Rank sum test. Rate of decline in lung function was adjusted for baseline lung function, age, sex. Results Bcc prevalence in CF is low in Belgium (<3%). 183 patients were included: 61 cases, 122 controls. 59% were F508del homozygous. Mean age in cases was 20.9 y (SD 10.5) vs 20.3 y (SD 10.3) in controls. Among the Bcc, 54% were unspecified, 31% were B. multivorans. Mean FEV1 at index year was 65.2% (SD 24.9) in cases vs 73.1 (SD 26.9) in controls (p = 0.07). FEV1 decline before index year was significantly higher in cases (–1.7%, SD 0.5) compared to controls (–1.0%, SD 0.3) (p = 0.002). FEV1 slopes were comparable in the period after index year (–1.1%, SD 0.5, in cases vs –0.99%, SD 0.4, p = 0.24). Conclusion Our results suggest that a declining FEV1 precedes acquisition of Bcc and may be a risk factor. After acquisition, lung function decline was comparable in Bcc infected and uninfected patients. These results should be interpreted with caution, since registry data are collected retrospectively and bear a risk of incompleteness or inaccuracy.

42 Comparison of 2 nasal potential difference measurement (NPD) methods (needle–abrasia): Is one more patient-friendly than the other?

NPD is a valuable diagnostic tool in case of questionable CF. Currently, 2 methods, that are considered equivalent, are used: (A) the Calomel/agar method using a needle as subcutaneous reference electrode (RE) and (B) the AgCl/ECG cream method using AgCl electrodes and ECG cream on abraded skin as RE. NPD is measured with a Marquat® catheter under the inferior turbinate (IT). Aim: To compare the subjects’ acceptance for the 2 methods. Methods: CF patients and healthy volunteers (HV) had method A and B in 2 nostrils on separate days. After each test they completed the questionnaire (Q): Did you experience pain at the RE site, at the IT site, during perfusion? Was the procedure annoying? Would you be prepared to repeat NPD? Which method do you prefer? Results: 50 Qs were completed by 12 CF patients (mean age 26.6 y) and 14 HV (mean age 24.7 y). 16/50 (10A/6B, 3CF/13HV) reported pain at RE site, 7/50 (4A/3B, 3CF/4HV) at IT site, and 1/50 (A, HV) during nasal perfusion. 12/50 (9A/3B, 8CF/4HV) found the procedure annoying. 37/50 would agree to repeat NPD, 13/50 probably would. 9/24 subjects (3CF/6HV) preferred method A, 5/24 (2CF/3HV) method B and 10/24 (5CF/5HV) had no preference. 2nd testing (B) was refused twice (2CF) for reasons not related to the test. CF patients reported less pain at RE site compared to HV (p = 0.017). No other statistical difference was found between both tests or between subject groups. Discussion: Overall, NPD was well tolerated. CF patients reported less pain at RE site compared to HV. Both methods were equally accepted by the study subjects. Further analyses of the quality of the tracings is needed to decide which method is most accurate.

388 Detection of a novel CFTR mutation c.122C>G (p.Pro41Arg) in a young cystic fibrosis (CF) patient with recurrent respiratory symptoms

Background: At present more than 1800 mutations have been described in the CFTR-gene. Several rare mutations are believed to cause mild lung disease and late onset of symptoms. We present a 5 y old Belgian boy heterozygous for an atypical CFTR variant and a novel variant which was never described before. Case report: A 5 y old boy with recurrent bronchitis and chronic sinusitis was referred to our clinic with repeated abnormal sweat chloride (Cl) (right 70mEq/L; left 53mEq/L) and elevated sweat sodium values (right 86mEq/L; left 62mEq/L), performed by Gibson and Cooke gauze method. Chest CT scan showed bronchial wall thickening and mucous plugging, without bronchiectasis. He is pancreatic sufficient, without history of pancreatitis. By screening the coding region of CFTR, using sequencing and MLPA (Multiplex Ligation-dependent Probe Amplification), he was shown to be heterozygous for c.224G>A (p.Arg75Gln − legacy name: R75Q) and c.122C>G (p.Pro41Arg), a novel variant which was never described before. Analysis of the parents is ongoing to prove that both variants are on different alleles. Discussion: R75Q is described as a variant overrepresented in patients with atypical CF, sarcoidosis, COPD and chronic pancreatitis and rather influences bicarbonate conductance than Cl. Our young patient has already respiratory symptoms and abnormal sweat chloride values. To our knowledge CFTR p.Pro41Arg has never been described before and its clinical relevance is not clear. As this boy has signs and symptoms of CF disease in combination with an atypical CFTR mutation, this novel mutation might be involved. However, mutations outside the coding region cannot be excluded.