Exhaled Breath Temperature as a Novel Marker of Future Development of COPD: Results of a Follow-Up Study in Smokers

Figures & data

Table 1. Characteristics of patients at initial visit according to sex (N = 140).

Variable^*	All (N = 140)	Women (n = 76)	Men (n = 64)	Statistics†
Age (years)	53.0 ± 6.4	53.5 ± 5.9	52.4 ± 6.9	t = 1.042; p = 0.299
BMI (kg/m^2)	26.58 ± 3.97	25.89 ± 3.97	27.40 ± 3.83	t = 2.274; p = 0.025
Pack-years	38.5 ± 17.9	33.2 ± 15.0	44.7 ± 19.3	t = 3.970; p < 0.001
FVC (%Pred, SR)	111.38 ± 15.41, 0.84 ± 1.14	113.35 ± 16.54, 0.96 ± 1.18	108.93 ± 13.63, 0.70 ± 1.07	t = 1.870; p = 0.064, t = 1.370; p = 0.173
FEV1 (%Pred, SR)	100.42 ± 13.60, 0.03 ± 0.96	100.54 ± 14.12, 0.04 ± 0.98	100.27 ± 13.04, 0.03 ± 0.95	t = 0.116; p = 0.908, t = 0.061; p = 0.951
FEV1/FVC (ratio, SR)	0.749 ± 0.064, −0.51 ± 0.94	0.759 ± 0.060, −0.47 ± 0.97	0.738 ± 0.066, −0.55 ± 0.91	t = 1.918; p = 0.057, t = 0.492; p = 0.623
PB FVC (%Pred, SR)	109.94 ± 14.51, 0.74 ± 1.07	111.92 ± 15.03, 0.83 ± 1.07	107.54 ± 13.60, 0.63 ± 1.06	t = 1.773; p = 0.078, t = 1.113; p = 0.268
PB FEV1 (%Pred, SR)	101.24 ± 13.96, 0.09 ± 0.97	101.12 ± 14.38, 0.08 ± 0.98	101.38 ± 13.54, 0.10 ± 0.97	t = 0.104; p = 0.918, t = 0.128; p = 0.898
PB FEV1/FVC (ratio, SR)	0.763 ± 0.062, −0.28 ± 0.91	0.771 ± 0.054, −0.25 ± 0.88	0.753 ± 0.068, −0.32 ± 0.95	t = 1.661; p = 0.099, t = 0.398; p = 0.691
ΔPB FEV1 (%)	1.28 ± 4.99	1.04 ± 3.59	1.54 ± 6.19	t = 0.477; p = 0.635
6MWT (%Pred)	64.25 ± 13.49	67.44 ± 11.31	60.39 ± 14.95	t = 2.878; p = 0.005
EBTb (°C)	33.33 ± 2.30	32.94 ± 2.67	33.80 ± 1.67	Z = 1.108; p = 0.268
EBTc (°C)	33.22 ± 2.10	32.79 ± 2.56	33.81 ± 0.96	Z = 1.207; p = 0.227
ΔEBT (°C)	−0.07 ± 1.42	−0.13 ± 1.45	0.01 ± 1.40	Z = 0.755; p = 0.755

Legend: ^*all values are presented as mean ± SD; †statistical significance was tested using Student's t-test (t value) or Mann-Whitney U-test (Z value); BMI – body mass index (calculated as weight in kg divided by the squared height in m); FVC – forced vital capacity as % predicted (%Pred) or as standardized residuals (SR); FEV₁ - forced expiratory volume in 1 second as % predicted (%Pred) or as standardized residuals (SR); FEV₁/FVC as ratio or as standardized residuals (SR); PB – postbronchodilator value; Δ – % change after bronchodilator; 6MWT – 6-minute walk test as % predicted (%Pred); EBT – exhaled breath temperature; EBTb – baseline EBT; EBTc – EBT after smoking cigarette; ΔEBT – change in EBT after smoking cigarette.

Figure 1. Association of EBTb with age (N = 140). Figure presents the association between the age (years) and the baseline exhaled breath temperature (EBTb), measured at the initial visit (Spearman R = −0.143, p = 0.092).

Figure 2. Association of ΔEBT with age (N = 140). Figure presents the association between the age (years) and the change in exhaled breath temperature after smoking cigarette (ΔEBT), measured at the initial visit (Spearman R = −0.069, p = 0.448).

Table 2. Characteristics of patients at the initial visit according to the pulmonologist assessment following GOLD guidelines (N = 140).

	Classification of patients
Variable^*	Asymptomatic (n = 37)	Symptomatic (n = 81)	COPD GOLD 1 (n = 22)	Statistics†	COPD LLN (n = 13)
Age (years)	52.2 ± 6.4	53.6 ± 6.4	52.1 ± 6.7	F = 0.876; p = 0.419	51.4 ± 5.7
Pack-years	36.6 ± 19.1	38.9 ± 17.9	39.6 ± 16.9	F = 0.255; p = 0.775	37.9 ± 15.9
PB FVC (SR)	0.76 ± 1.01	0.69 ± 1.08	0.86 ± 1.14	F = 0.219; p = 0.804	0.51 ± 1.24
PB FEV1 (SR)	0.18 ± 0.98	0.25 ± 0.86	−0.62 ± 1.06	F = 8.246; p < 0.001	−1.09 ± 1.12
PB FEV1/FVC (SR)	−0.26 ± 0.76	0.08 ± 0.71	−1.60 ± 0.44	F = 53.879; p < 0.001	−1.95 ± 0.30^††
6MWT (%Pred)	63.74 ± 13.37	64.04 ± 14.26	66.15 ± 10.60	F = 0.186; p = 0.813	57.83 ± 12.43^††
CAT score	5.2 ± 4.6	10.1 ± 6.7	13.1 ± 8.8	H = 21.520; p < 0.001	11.9 ± 5.8
SGRQ symptom score	12.3 ± 17.6	21.3 ± 16.3	30.5 ± 25.6	H = 17.566; p < 0.001	26.2 ± 19.0
SGRQ activity score	23.6 ± 15.2	26.0 ± 17.6	26.6 ± 19.9	H = 15.628; p < 0.001	23.8 ± 16.6
SGRQ impact score	3.7 ± 8.1	7.2 ± 9.1	11.5 ± 11.2	H = 11.293; p = 0.004	10.7 ± 9.4
SGRQ total score	8.2 ± 10.7	15.2 ± 10.4	19.2 ± 13.9	H = 19.686; p < 0.001	17.2 ± 10.0
EBTb (°C)	32.56 ± 3.66	33.98 ± 1.64	32.89 ± 3.47	F = 0.353; p = 0.703	33.96 ± 1.08
EBTc (°C)	32.66 ± 2.81	33.74 ± 1.71	32.82 ± 3.29	F = 1.248; p = 0.291	33.64 ± 0.88
ΔEBT (°C)	0.10 ± 2.00	−0.24 ± 0.63	−0.07 ± 1.48	F = 0.001; p = 0.999	−0.25 ± 1.33

Legend: ^*all values are presented as mean ± SD; †statistical significance for comparison between three groups according to GOLD was tested using analysis of variance (ANOVA, F value) or Kruskal-Wallis ANOVA (H value); ††significantly different to COPD GOLD 1 (p < 0.05); COPD: chronic obstructive pulmonary disease; GOLD: Global Initiative for Chronic Obstructive Lung Disease; PB – postbronchodilator value; FVC – forced vital capacity as standardized residuals (SR); FEV₁ – forced expiratory volume in 1 second as standardized residuals (SR); FEV₁/FVC as standardized residuals (SR); 6MWT – 6-minute walk test as % predicted (%Pred); CAT – COPD assessment test; SGRQ – St. George Respiratory Questionnaire; EBT – exhaled breath temperature; EBTb – baseline EBT; EBTc – EBT after smoking cigarette; ΔEBT – change in EBT after smoking cigarette.

Table 3. EBT (EBTb, EBTc and ΔEBT) according to the outcomes of disease progression after 2-year follow-up (N = 140).

Disease progression outcome			EBTb (°C)	EBTc (°C)	ΔEBT (°C)
ND COPD	GOLD	No (n = 111); Yes (n = 7); Statistics^†	33.41 ± 2.17; 31.02 ± 4.14; Z = 1.419, p = 0.156	33.18 ± 2.21; 32.56 ± 2.80; Z = 0.601, p = 0.548	−0.20 ± 1.23; 1.54 ± 2.85; Z = 1.446, p = 0.148
	LLN	No (n = 113); Yes (n = 5); Statistics^†	33.43 ± 2.23; 30.17 ± 3.03; Z = 2.348, p = 0.019	33.25 ± 2.10; 30.98 ± 3.87; Z = 1.518, p = 0.129	−0.28 ± 1.05; 2.72 ± 2.43; Z = 2.099, p = 0.036
DP	GOLD	No (n = 129); Yes (n = 11); Statistics^†	33.51 ± 2.05; 31.29 ± 3.85; Z = 1.758, p = 0.079	33.27 ± 2.05; 32.71 ± 2.63; Z = 0.320, p = 0.749	−0.21 ± 1.21; 1.46 ± 2.51; Z = 2.170, p = 0.030
	LLN	No (n = 131); Yes (n = 9); Statistics^†	33.51 ± 2.11; 31.01 ± 3.39; Z = 2.249, p = 0.024	33.35 ± 1.96; 31.45 ± 3.19; Z = 2.175, p = 0.030	−0.16 ± 1.30; 1.12 ± 2.42; Z = 1.827, p = 0.067
Increased LoLF	Loss of FEV1 >70 ml/year	No (n = 80); Yes (n = 60); Statistics^†	33.49 ± 2.05; 33.23 ± 2.56; Z = 0.543, p = 0.587	33.20 ± 2.18; 33.29 ± 2.02; Z = 0.020, p = 0.984	−0.20 ± 1.34; 0.13 ± 1.57; Z = 0.104, p = 0.917
	Loss of FEV1 >1 SR	No (n = 126); Yes (n = 14); Statistics^†	33.35 ± 2.32; 33.18 ± 2.18; Z = 0.802, p = 0.422	33.25 ± 2.18; 33.02 ± 2.49; Z = 0.159, p = 0.874	−0.07 ± 1.47; −0.10 ± 0.96; Z = 0.059, p = 0.953

Legend: ND COPD – newly diagnosed COPD after 2 years of follow-up; DP – disease progression – ND COPD + progression of a severity of COPD from GOLD 1 stage during the 2-year follow-up; LoLF – loss of lung function; GOLD: Global Initiative for Chronic Obstructive Lung Disease; LLN: lower level of normal; FEV₁: Forced expiratory volume in 1 second; SR: standardized residuals; EBT – exhaled breath temperature; EBTb – baseline EBT; EBTc – EBT after smoking cigarette; ΔEBT – change in EBT after smoking cigarette; *values are presented as mean ± SD; †statistical significance was tested using Mann-Whitney U-test.

Table 4. EBT (EBTb, EBTc and ΔEBT) ROC curve analysis data according to the outcomes of disease progression after 2-year follow-up (N = 140).

Disease progression outcome			EBTb	EBTc	ΔEBT
ND COPD	GOLD	AUC, 95% CI, Statistics	0.664, 0.571–0.748, Z = 1.199, p = 0.231	0.568, 0.466–0.667, Z = 0.547, p = 0.584	0.669, 0.568–0.759, Z = 1.409, p = 0.159
	LLN	AUC, 95% CI, Statistics	0.788, 0.703–0.858, Z = 2.330, p = 0.020	0.704, 0.605–0.791, Z = 1.124, p = 0.261	0.859, 0.781–0.917, Z = 2.533, p = 0.011
DP	GOLD	AUC, 95% CI, Statistics	0.663, 0.579–0.740, Z = 1.595, p = 0.111	0.530, 0.438–0.621, Z = 0.274, p = 0.784	0.711, 0.622–0.789, Z = 2.404, p = 0.016
	LLN	AUC, 95% CI, Statistics	0.716, 0.634–0.789, Z = 2.246, p = 0.025	0.731, 0.644–0.808, Z = 1.993, p = 0.046	0.614, 0.520–0.702, Z = 0.783, p = 0.433

Legend: ND COPD – newly diagnosed COPD after 2 years of follow-up; DP - disease progression – ND COPD + progression of a severity of COPD from GOLD 1 stage during the 2-year follow-up; GOLD: Global Initiative for Chronic Obstructive Lung Disease; LLN: lower level of normal; AUC: area under the curve; CI: confidence interval; EBT – exhaled breath temperature; EBTb – baseline EBT; EBTc – EBT after smoking cigarette; ΔEBT – change in EBT after smoking cigarette; statistical significance was tested using z statistics.