Open Access

'Diagnosing Asthma in General Practice with Portable Exhaled Nitric Oxide Measurement – Results of a Prospective Diagnostic Study: FENO ≤ 16 ppb better than FENO ≤ 12 ppb to rule out mild and moderate to severe asthma

Respiratory Research200910:64

https://doi.org/10.1186/1465-9921-10-64

Received: 01 July 2009

Accepted: 07 July 2009

Published: 07 July 2009

Correction

In our study to evaluate the diagnostic accuracy of FENO measurement with NioxMino® for the diagnosis of asthma in general practice, we found the cut-off at FENO ≤ 12 ppb to rule out mild and moderate to severe asthma with a negative predictive value of 81% (95%CI 64–91%) [1]. We oriented ourselves at the already established value of 12 ppb [2]. However, we overlooked in the ROC analysis that the overall diagnostic accuracy improves slightly when the cut-off is chosen at FENO ≤ 16 ppb (revised table two) [see table 1]. Negative likelihood ratio was 0.38 (95%CI 0.22–0.64) and positive likelihood ratio was 1.76 (95%CI 1.37–2.26) using the 16 ppb cut-off (revised table three) [see Table 2].
Table 1

Sensitivity (sens), specificity (spec), positive predictive value (PPV) and negative predictive value (NPV) at different cut-off points (n = 160); unit of FENO is parts per billion

Asthma diagnoses

FENO

sens [%] (95%CI)

spec [%] (95%CI)

PPV [%] (95%CI)

NPV [%] (95%CI)

n

Borderline BHR mild BHR moderate to severe BHR positive bronchodilator reversibility

(n = 75)*

> 12

85 (76–92)

24 (16–34)

50 (41–58)

65 (47–79)

126

 

> 16

69 (58–79)

53 (42–63)

57 (46–66)

66 (54–76)

92

 

> 20

64 (53–74)

58 (47–77)

57 (47–67)

65 (53–74)

82

 

> 35

32 (25–42)

84 (74–90)

63 (47–77)

58 (49–67)

38

 

> 46

32 (23–43)

93 (85–97)

80 (63–91)

61 (52–69)

30

 

> 76

13 (7–23)

100 (96–100)

100 (72–100)

57 (49–65)

11

Mild BHR moderate to severe BHR positive bronchodilator reversibility

(n = 58)§

> 12

90 (79–95)

25 (17–34)

40 (32–49)

81 (64–91)

126

 

> 16

79 (67–88)

55 (45–64)

50 (40–60)

82 (72–90)

92

 

> 20

67 (54–78)

62 (52–71)

50 (39–61)

77 (67–85)

82

 

> 35

36 (25–49)

83 (75–89)

55 (40–70)

70 (61–77)

38

 

> 46

36 (25–49)

91 (84–95)

70 (52–83)

72 (63–79)

30

 

> 76

17 (10–29)

100 (96–100)

100 (72–100)

68 (60–75)

11

*prevalence of asthma = 46.9%, prevalence of 'no asthma' = 53.1%

§ prevalence of asthma = 36,3%, prevalence of 'no asthma' = 63.7%

Table 2

Likelihood ratio at different cut-off points (n = 160); unit of FENO is parts per billion; LR+ is positive likelihood ratio, LR- is negative likelihood ratio

Asthma diagnoses

FENO

LR+ (95%CI)

LR- (95%CI)

Borderline BHR, mild BHR, moderate to severe BHR, positive bronchodilator reversibility (n = 75)

> 12

1.12 (0.96–1.30)

0.62 (0.32–1.21)

 

> 16

1.47 (1.12–1.93)

0.58 (0.39–0.86)

 

> 20

1.55 (1.12–2.14)

0.65 (0.47–0.91)

 

> 35

1.94 (1.09–3.48)

0.81 (0.68–0.98)

 

> 46

4.53 (1.96–10.49)

0.73 (0.62–0.86)

 

> 76

not calculable

not calculable

Mild BHR, moderate to severe BHR, positive bronchodilator reversibility (n = 58)

> 12

1.19 (1.03–1.37)

0.42 (0.18–0.97)

 

> 16

1.76 (1.37–2.26)

0.38 (0.22–0.64)

 

> 20

1.76 (1.30–2.39)

0.53 (0.36–0.79)

 

> 35

2.17 (1.25–3.77)

0.77 (0.62–0.95)

 

> 46

4.10 (2.02–8.36)

0.70 (0.57–0.86)

 

> 76

not calculable

not calculable

In patients with unsuspicious spirometric results (n = 101; not in table) there was no improvement of diagnostic accuracy. The best cut-off point was at FENO ≤ 16 ppb again. In this diagnostic group sensitivity was 78% (95%CI 63–89%), specificity was 45% (95%CI 34–57%), PPV was 45% (95%CI 34–57%) and NPV was 78% (95%CI 63–89%).

Table two [see Table 1 below] illustrates that the patient group with correctly excluded asthma by FENO measurement increases at FENO ≤ 16 ppb; and the range of the confidence interval narrows. Thus three patients need to be diagnosed for excluding asthma in order to save one bronchial provocation test when FENO ≤ 16 ppb is used as the cut-off point. With FENO ≤ 12 ppb five patients need to be tested in order to exclude asthma in one of them. Therefore, we suggest choosing FENO ≤ 16 ppb to rule out mild and moderate to severe asthma. This improves diagnostic efficiency compared to the ≤ 12 ppb cut-off point.

We would like to correct the following points in the manuscript:

In the Results section of the Abstract lines 6–7 should read as:

"16 ppb (n = 68; 42.5%), sensitivity was 79% (95%CI 67–88), specificity 55% (95%CI 45–64), PPV 50% (95%CI 40–60), NPV 82% (95%CI 72–90)".

Also in line 7, "Three" should say "Two".

In the Conclusion section of the Abstract, in line 2, "FENO ≤ 12 ppb" should say "FENO ≤ 16 ppb".

In the Sensitivity analyses section, in line 2 of the third paragraph, "FENO ≤ 12 ppb" should say "FENO ≤ 16 ppb", "81% (95% CI 64–91)" should say "82% (95% CI 72–90)" and "34" should say "68". In line 3, "FENO ≤ 12 ppb" should say "FENO ≤ 16 ppb" and "five" should say "three". In line 4 "12 ppb" should say "16 ppb". The sentence starting in line 5 and ending in line 6 should read: "Sensitivity was 78% (95%CI 63–89), specificity was 45% (95%CI 34–57), PPV was 45% (95%CI 34–57), NPV was 78 (95%CI 63–89)". In line 6, "16 (15.8%)" should say "37 (36.6%)", "FENO ≤ 12 ppb" should say "FENO ≤ 16 ppb" and "increased up to 82% (95%CI 64–92)" should say "was 77% (95%CI 61–88)".

In the Discussion section, in line 4, "81%" should say "82%" and in line 5, "FENO ≤ 12" should say "FENO ≤ 16"

In the second paragraph, in line 1, "five" should say "three". In line 5, "16 patients had FENO ≤ 12 ppb" should say "37 patients had FENO ≤ 16 ppb". Also in line 5, "three" should say "two" and in lines 11 and 12 "FENO ≤ 12 ppb" should say ""FENO ≤ 16 ppb" and 12 ppb<FENO should say 16 ppb<FENO.

In the third line of the third paragraph "12 to 46 ppb" should say "16 to 46 ppb" and in the seventh line, the second half of the sentence that reads "and the difference of the 95%CI (-9.8 ppb) and 20 ppb is close to our best cut-off point (12 ppb) to rule out asthma" should not be there.

In the conclusion section, in line 3 "FENO ≤ 12 ppb" should say ""FENO ≤ 16 ppb" and "three" should say "two".

Authors’ Affiliations

(1)
Department of General Practice and Health Services Research, University Hospital, University of Heidelberg
(2)
Department of Primary Care Medicine, Radboud University Nijmegen Medical Centre
(3)
Department of Cardiology, Pulmonology and Angiology, Medical Centre, University of Heidelberg

References

  1. Schneider A, Tilemann L, Schermer T, Gindner L, Laux G, Szecsenyi J, Meyer FJ: Diagnosing asthma in general practice with portable exhaled nitric oxide measurement – results of a prospective diagnostic study. Respir Res 2009, 10:15.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Menzies D, Nair A, Lipworth BJ: Portable exhaled nitric oxide measurement: Comparison with the "gold standard" technique. Chest 2007, 131:410–414.View ArticlePubMedGoogle Scholar

Copyright

© Schneider et al. 2009

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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