Limits...
Intestinal current measurement versus nasal potential difference measurements for diagnosis of cystic fibrosis: a case-control study.

Bagheri-Hanson A, Nedwed S, Rueckes-Nilges C, Naehrlich L - BMC Pulm Med (2014)

Bottom Line: The NPD CFTR response to Cl-free and isoproterenol perfusion (Δ0Cl- + Iso) was compared to the ICM CFTR response to forskolin/IBMX, carbachol, and histamine (ΔIsc, forskolin/IBMX+ carbachol+histamine).Smokers have a decreased CFTR response measured by NPD (p = 0.049).For ICM there is a trend towards decreased CFTR response (NS).

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Justus-Liebig-University Giessen, Feulgenstrasse 12, 35385 Giessen, Germany. lutz.naehrlich@paediat.med.uni-giessen.de.

ABSTRACT

Background: Nasal potential difference (NPD) and intestinal current measurement (ICM) are functional CFTR tests that are used as adjunctive diagnostic tools for cystic fibrosis (CF). Smoking has a systemic negative impact on CFTR function. A diagnostic comparison between NPD and ICM and the impact of smoking on both CFTR tests has not been done.

Methods: The sweat chloride test, NPD, and ICM were performed in 18 patients with CF (sweat chloride >60 mmol/l), including 6 pancreatic sufficient (PS) patients, and 13 healthy controls, including 8 smokers. The NPD CFTR response to Cl-free and isoproterenol perfusion (Δ0Cl- + Iso) was compared to the ICM CFTR response to forskolin/IBMX, carbachol, and histamine (ΔIsc, forskolin/IBMX+ carbachol+histamine).

Results: The mean NPD CFTR response and ICM CFTR response between patients with CF and healthy controls was significantly different (p <0.001), but not between patients with CF who were PS and those who were pancreatic insufficient (PI). Smokers have a decreased CFTR response measured by NPD (p = 0.049). For ICM there is a trend towards decreased CFTR response (NS). Three healthy control smokers had NPD responses within the CF-range. In contrast to NPD, there was no overlap of the ICM response between patients with CF and controls.

Conclusions: ICM is superior to NPD in distinguishing between patients with CF who have a sweat chloride > 60 mmol/l and healthy controls, including smokers. Neither NPD nor ICM differentiated between patients with CF who were PS from those who were PI. Smoking has a negative impact on CFTR function in healthy controls measured by NPD and challenges the diagnostic interpretation of NPD, but not ICM.

Show MeSH

Related in: MedlinePlus

Correlation of average Δ0Cl- + Iso (NPD) and sweat chloride. The normal range is indicated for values below and left of the dotted lines, and the intermediate range is shown between the solid and dotted lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4199064&req=5

Fig1: Correlation of average Δ0Cl- + Iso (NPD) and sweat chloride. The normal range is indicated for values below and left of the dotted lines, and the intermediate range is shown between the solid and dotted lines.

Mentions: Our study included 18 patients with CF and 13 healthy controls with a median age of 20.5 and 25.0 years, respectively (NS) (Table 1). As consequence of our inclusion criteria, sweat chloride values distinguish patients with CF from healthy controls (p < 0.001). Although the mean sweat chloride differed between CF-PS and CF-PI patients (p = 0.003), an individual overlap occurs (Table 1, Figure 1). The mean NPD CFTR response significantly discriminated between CF patients and healthy controls (p <0.001), but not between patients with CF who were PS versus PI (Table 1). Four healthy controls had an average Δ0Cl- + Iso of > -7.7 mV. Three out of four controls had a repeatable average NPD CFTR response in the CF-range for Δ0Cl- + Iso > -7.7 mV (23% of all healthy controls) (Figure 1), and two additional controls when using the Wilschanski score (15% of all healthy controls) (Figure 2). All these healthy controls were smokers. CFTR genotyping was offered to these three healthy controls as part of clinical routine and none had two CF-causing mutations (Table 1). For ICM a median of 6 (5–7) rectal biopsies were sampled per patient without severe adverse events. The mean ICM CFTR response was significantly different between CF patients and healthy controls (p <0.001), but not between patients with CF who were PS versus those who were PI (Table 1). We could not detect any age-dependency of the response to Isoproterenol/Forskolin. In contrast to NPD, there was no overlap between CF-patients and controls (Figures 3 and 4). Using the best instead of the average NPD, the CFTR response overlap did not change (Additional file 1). Using the best instead of the average ICM, the CFTR response resulted in one overlap (Additional file 2).Table 1


Intestinal current measurement versus nasal potential difference measurements for diagnosis of cystic fibrosis: a case-control study.

Bagheri-Hanson A, Nedwed S, Rueckes-Nilges C, Naehrlich L - BMC Pulm Med (2014)

Correlation of average Δ0Cl- + Iso (NPD) and sweat chloride. The normal range is indicated for values below and left of the dotted lines, and the intermediate range is shown between the solid and dotted lines.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4199064&req=5

Fig1: Correlation of average Δ0Cl- + Iso (NPD) and sweat chloride. The normal range is indicated for values below and left of the dotted lines, and the intermediate range is shown between the solid and dotted lines.
Mentions: Our study included 18 patients with CF and 13 healthy controls with a median age of 20.5 and 25.0 years, respectively (NS) (Table 1). As consequence of our inclusion criteria, sweat chloride values distinguish patients with CF from healthy controls (p < 0.001). Although the mean sweat chloride differed between CF-PS and CF-PI patients (p = 0.003), an individual overlap occurs (Table 1, Figure 1). The mean NPD CFTR response significantly discriminated between CF patients and healthy controls (p <0.001), but not between patients with CF who were PS versus PI (Table 1). Four healthy controls had an average Δ0Cl- + Iso of > -7.7 mV. Three out of four controls had a repeatable average NPD CFTR response in the CF-range for Δ0Cl- + Iso > -7.7 mV (23% of all healthy controls) (Figure 1), and two additional controls when using the Wilschanski score (15% of all healthy controls) (Figure 2). All these healthy controls were smokers. CFTR genotyping was offered to these three healthy controls as part of clinical routine and none had two CF-causing mutations (Table 1). For ICM a median of 6 (5–7) rectal biopsies were sampled per patient without severe adverse events. The mean ICM CFTR response was significantly different between CF patients and healthy controls (p <0.001), but not between patients with CF who were PS versus those who were PI (Table 1). We could not detect any age-dependency of the response to Isoproterenol/Forskolin. In contrast to NPD, there was no overlap between CF-patients and controls (Figures 3 and 4). Using the best instead of the average NPD, the CFTR response overlap did not change (Additional file 1). Using the best instead of the average ICM, the CFTR response resulted in one overlap (Additional file 2).Table 1

Bottom Line: The NPD CFTR response to Cl-free and isoproterenol perfusion (Δ0Cl- + Iso) was compared to the ICM CFTR response to forskolin/IBMX, carbachol, and histamine (ΔIsc, forskolin/IBMX+ carbachol+histamine).Smokers have a decreased CFTR response measured by NPD (p = 0.049).For ICM there is a trend towards decreased CFTR response (NS).

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Justus-Liebig-University Giessen, Feulgenstrasse 12, 35385 Giessen, Germany. lutz.naehrlich@paediat.med.uni-giessen.de.

ABSTRACT

Background: Nasal potential difference (NPD) and intestinal current measurement (ICM) are functional CFTR tests that are used as adjunctive diagnostic tools for cystic fibrosis (CF). Smoking has a systemic negative impact on CFTR function. A diagnostic comparison between NPD and ICM and the impact of smoking on both CFTR tests has not been done.

Methods: The sweat chloride test, NPD, and ICM were performed in 18 patients with CF (sweat chloride >60 mmol/l), including 6 pancreatic sufficient (PS) patients, and 13 healthy controls, including 8 smokers. The NPD CFTR response to Cl-free and isoproterenol perfusion (Δ0Cl- + Iso) was compared to the ICM CFTR response to forskolin/IBMX, carbachol, and histamine (ΔIsc, forskolin/IBMX+ carbachol+histamine).

Results: The mean NPD CFTR response and ICM CFTR response between patients with CF and healthy controls was significantly different (p <0.001), but not between patients with CF who were PS and those who were pancreatic insufficient (PI). Smokers have a decreased CFTR response measured by NPD (p = 0.049). For ICM there is a trend towards decreased CFTR response (NS). Three healthy control smokers had NPD responses within the CF-range. In contrast to NPD, there was no overlap of the ICM response between patients with CF and controls.

Conclusions: ICM is superior to NPD in distinguishing between patients with CF who have a sweat chloride > 60 mmol/l and healthy controls, including smokers. Neither NPD nor ICM differentiated between patients with CF who were PS from those who were PI. Smoking has a negative impact on CFTR function in healthy controls measured by NPD and challenges the diagnostic interpretation of NPD, but not ICM.

Show MeSH
Related in: MedlinePlus