Exhaled nitric oxide in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

Figures & data

Figure 1 Flow diagram of literature search and study selection.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 1 Characters of included studies

Study source	Study design	Study population	Gender (m/f)	Number of participants	COPD diagnosis	FENO measurement
Kanazawa et al,^Citation16 1998	CS	Japan	21/0	21	ATS	Chemiluminescence analyzer (CLM-500; Shimazu; Kyoto, Japan)
Rutgers et al,^Citation23 1998	CS	the Netherlands	25/7	32	Doctor-diagnosis	Chemiluminescence analyzer (CLD 700 AL, ECO physics, Dürnten, Switzerland)
Agusti et al,^Citation29 1999	CS	Spain	27/0	27	Doctor-diagnosis	Chemiluminescence analyzer (Dasibi Environmental, Glendale, CA, USA)
Corradi et al,^Citation28 1999	CS	Italy	32/18	50	BTS	Chemiluminescence NO analyzer (model 42S; Thermo Environmental Instruments Inc, Franklin, MA, USA)
Clini et al,^Citation11 2000	CS	Italy	17/2	19	ATS	Chemiluminescence analyzer (LR 2000 series; Logan Research; Kent, UK)
Delen et al,^Citation13 2000	CS	America	NA	77	Doctor-diagnosis	Chemiluminescence (model 280; Sievers Instruments; Boulder, CO, USA)
Papi et al,^Citation20 2000	CS	Italy	24/5	29	ERS	Chemiluminescence analyzer (NOA 280; Sievers)
Montuschi et al,^Citation19 2001	CS	United Kingdom	27/25	52	BTS	Chemiluminescence analyzer (model LR 2000; Logan Research; Rochester, UK)
Hogman et al,^Citation15 2002	CS	Sweden	NA	60	Doctor-diagnosis	280 chemiluminescence analyzer (Sievers)
Zietkowski et al,^Citation27 2005	CS	Poland	58/29	87	ERS	Chemiluminescence technique (Sievers 280i NO analyzer, Sievers)
Brindicci et al,^Citation10 2005	CS	United Kingdom	27/24	51	GOLD	Chemiluminescence analyzer (NIOXH; Aerocrine AB, Stockholm, Sweden)
Ziora et al,^Citation26 2007	CS	Poland	51/12	63	GOLD	Chemiluminescent NO analyzer (model 280, Sievers Instruments)
Liu et al,^Citation17 2007	CS	Australia	NA	176	Doctor-diagnosis	Chemiluminescent NO analyzer (Dasibi Environmental Corp.)
de Laurentiis et al,^Citation12 2008	CS	Italy	NA	69	GOLD	Electrochemical FENO device (NIOX MINO, Aerocrine)/chemiluminescence analyzer (NOA, Sensormedics, Milano, Italy)
Beg et al,^Citation31 2009	CS	Saudi Arabia	39/0	39	Doctor-diagnosis	Chemiluminescence analyzer (SERES, Aix-en-Provence, France)
Lehouck et al,^Citation33 2010	CC	Belgium	121/30	151	GOLD	Chemiluminescence analyzer (NIOX, Flex; Aerocrine AB)
Rouhos et al,^Citation22 2011	CS	Finland	18/21	39	Doctor-diagnosis	Chemiluminescence analyzer (Sievers 270B, Sievers)
Maricic et al,^Citation18 2013	CS	Croatia	NA	100	GOLD	NA
Sun et al,^Citation25 2013	CS	People’s Republic of China	35/10	45	CMA	The 4540-1999b portable nitric oxide gas detector (Interscan Corporation, Simi Valley, CA USA)
Hirano et al,^Citation14 2013	CS	Japan	24/12	36	GOLD	Chemiluminescence-based NO analyzer NA-623N, (Chest Co. and Kimoto Electric Co., Tokyo, Japan)
Moussa et al,^Citation32 2014	CC	Tunisia	45/0	45	Doctor-diagnosis	Electrochemical analyzer (Medisoft, Dinant, Belgium)
Rawy and Mansour,^Citation21 2015	CS	Egypt	61/29	90	Doctor-diagnosis	Niox Mino analyzer (Aerocrine AG)
Santini et al,^Citation30 2016	CS	Italy	67/22	99	GOLD	NIOX system (Aerocrine)
Shrestha et al,^Citation24 2017	CS	Nepal	91/121	212	GOLD	Handheld Bedfont NO breath point-of-care device (Bedfont Scientific Ltd, Maidstone, Kent, UK, registered in England and Wales)

Abbreviations: ATS, American Thoracic Society criteria; BTS, British Thoracic Society guidelines; CC, case–control study; CMA, Chinese Medical Association guidelines; COPD, chronic obstructive pulmonary disease; CS, cross-sectional study; ERS, European Respiratory Society criteria; FENO, fractional exhaled nitric oxide; GOLD, Global Initiative for Obstructive Lung Disease; NA, not available.

Table 2 Subgroup analyses

	Studies (n)	Participants	SMD (95% CI)	I^2 (%)
Total	24	1,669	1.28 (0.60–1.96)	96
Subgroup
COPD status
Stable	20	1,393	1.21 (0.47–1.96)	96
Exacerbated	2	53	3.20 (−3.22 to 9.61)	97
Smoking status in COPD ex-smokers/current smokers
COPD	7	323	2.05 (1.13–2.97)	90

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; SMD, standard mean difference.

Figure 2 Comparison of FENO levels between COPD patients and controls in the included studies.

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FENO, fractional exhaled nitric oxide; IV, inverse variance; SMD, standard mean deviation; SD, standard deviation.

Figure 3 Comparison of fractional exhaled nitric oxide levels between stable/exacerbated COPD patients and controls.

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; FENO, fractional exhaled nitric oxide; IV, inverse variance; SMD, standard mean deviation; SD, standard deviation.

Figure 4 Comparison of FENO levels between ex-smokers and current smokers.

Abbreviations: CI, confidence interval; FENO, fractional exhaled nitric oxide; IV, inverse variance; SMD, standard mean deviation; SD, standard deviation.

Figure S1 Sensitivity analysis of included studies by omitting each study.

Figure S2 Funnel plot of exhaled nitric oxide in COPD.

Abbreviations: SE, standard error; SMD, standard mean difference.

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