Defining Chronic Mucus Hypersecretion Using the CAT in the SPIROMICS Cohort

Figures & data

Table 1 Questions for Determination of Various Definitions of CMH

Definition	Description
MRC-CMH	Cough on most days for ≥3 consecutive months or more during the year AND phlegm from chest on most days for ≥3 consecutive months or more during the year
MRC-CB	Cough on most days for ≥3 consecutive months or more during the year AND phlegm from chest on most days for ≥3 consecutive months or more during the year, with these symptoms for ≥2 consecutive years
SGRQ- CMH	Cough for most days or several days a week (option 1 or 2 for the “I cough” question) AND phlegm for most days or several days a week (option 1 or 2 for the “I bring up phlegm [sputum]” question)
CAT-CMH	Multiple permutations of cut-points of 2 or 3 for cough and phlegm questions were explored to determine optimal CAT-CMH definition. Scores spanned 0 to 5, from “I never cough” to “I cough all the time” and from “I have no phlegm in my chest at all” to “My chest is full of phlegm”

Abbreviations: CAT, COPD Assessment Test; CB, chronic bronchitis; CMH, chronic mucus hypersecretion; MRC, Medical Research Council; SGRQ, St. George’s Respiratory Questionnaire.

Table 2 Frequency of CMH by Multiple Definitions

CMH Definition	N	n CMH+	n CMH−
MRC-CMH	1044	398 (38%)	646 (62%)
MRC-CB	1386	326 (24%)	1064 (76%)
SGRQ-CMH	1361	639 (47%)	722 (53%)
CAT-CMH: Cough Q and Phlegm Q both ≥3	1407	348 (25%)	1059 (75%)
CAT-CMH: Cough Q and Phlegm Q both ≥2	1407	686 (49%)	721 (51%)

Abbreviations: CAT, COPD Assessment Test; CB, chronic bronchitis; CMH, chronic mucus hypersecretion; SGRQ, MRC, Medical Research Council; St. George’s Respiratory Questionnaire.

Table 3 Evaluation of Different CAT Cut-Points Using SGRQ-CMH and MRC-CMH as Gold Standard

CAT vs MRC-CMH	Sensitivity	Specificity	PPV	NPV	Kappa
Cough Q and Phlegm Q both ≥3	59%	90%	78%	78%	0.51
Cough Q and Phlegm Q both ≥2	87%	72%	66%	90%	0.56
Cough Q ≥2 and Phlegm Q ≥3	67%	87%	77%	81%	0.55
Cough Q ≥3 and Phlegm Q ≥2	70%	85%	74%	82%	0.55
Only Cough Q ≥3	73%	82%	71%	83%	0.54
Only Phlegm Q ≥3	68%	85%	74%	81%	0.54
Only Cough Q ≥2	93%	57%	57%	93%	0.44
Only Phlegm Q ≥2	90%	64%	60%	91%	0.49
CAT vs SGRQ-CMH	Sensitivity	Specificity	PPV	NPV	Kappa
Cough Q and Phlegm Q both ≥3	49%	95%	90%	68%	0.45
Cough Q and Phlegm Q both ≥2	80%	78%	77%	82%	0.58
Cough Q ≥2 and Phlegm Q ≥3	56%	92%	85%	70%	0.48
Cough Q ≥3 and Phlegm Q ≥2	60%	91%	86%	72%	0.52
Only Cough Q ≥3	63%	86%	80%	73%	0.50
Only Phlegm Q ≥3	57%	90%	83%	70%	0.48
Only Cough Q ≥2	88%	59%	65%	85%	0.46
Only Phlegm Q ≥2	85%	69%	71%	84%	0.53

Abbreviations: CAT, COPD Assessment Test; CMH, chronic mucus hypersecretion; MRC, Medical Research Council; NPV, negative predictive value; PPV, positive predictive value; SGRQ, St. George’s Respiratory Questionnaire.

Table 4 Demographics and Clinical Characteristics of CMH+ and CMH− Participants, Based on SGRQ and CAT Definitions at Baseline

Characteristics, n (%)	Entire Cohort N=1431	SGRQ		CAT
		CMH+ N=639	CMH− N=722	CMH+ N=686	CMH− N=721
Age, years
40–49	36 (2.5%)	17 (2.7%)	18 (2.5%)	22 (3.2%)	13 (1.8%)
50–59	322 (22.5%)	190 (29.7%)	120 (16.6%)	195 (28.4%)	116 (16.1%)
60–69	587 (41.0%)	244 (38.2%)	313 (43.4%)	260 (37.9%)	323 (44.8%)
70–79	486 (34.0%)	188 (29.4%)	271 (37.5%)	209 (30.5%)	269 (37.3%)
Sex
Male	822 (57.4%)	383 (59.9%)	403 (55.8%)	384 (56.0%)	428 (59.4%)
Female	609 (42.6%)	256 (40.1%)	319 (44.2%)	302 (44.0%)	293 (40.6%)
Tobacco history
Current smoker	484 (34.4%)	321 (51.0%)	138 (19.4%)	333 (49.5%)	140 (19.7%)
Ex-smoker	924 (65.6%)	308 (49.0%)	574 (80.6%)	340 (50.5%)	572 (80.3%)
Smoking number pack-years (mean, SD)	53.9 (43.4)	53.5 (26.5)	54.3 (55.3)	55.5 (55.3)	52.3 (28.2)
FEV1% predicted (mean, SD)	60.8 (23.0)	58.1 (21.1)	62.8 (24.2)	57.8 (21.0)	63.8 (24.2)
GOLD grade of airflow limitation
Grade 1	306 (21.4%)	100 (15.6%)	187 (25.9%)	103 (15.0%)	199 (27.6%)
Grade 2	640 (44.7%)	314 (49.1%)	292 (40.4%)	337 (49.1%)	296 (41.1%)
Grade 3	338 (23.6%)	155 (24.3%)	173 (24.0%)	174 (25.4%)	155 (21.5%)
Grade 4	147 (10.3%)	70 (11.0%)	70 (9.7%)	72 (10.5%)	71 (9.8%)
GOLD 2017 Grade
A	325 (24.9%)	75 (12.7%)	232 (35.0%)	45 (7.0%)	280 (42.0%)
B	728 (55.7%)	386 (65.4%)	319 (48.1%)	438 (68.4%)	290 (43.5%)
C	22 (1.7%)	5 (0.8%)	16 (2.4%)	2 (0.3%)	20 (3.0%)
D	231 (17.7%)	124 (21.0%)	96 (14.5%)	155 (24.2%)	76 (11.4%)
BMI
<18.5	35 (2.5%)	24 (3.8%)	11 (1.6%)	21 (3.1%)	13 (1.9%)
18.5 to <25	457 (32.7%)	192 (30.8%)	238 (33.8%)	226 (33.5%)	223 (31.9%)
25 to <30	479 (34.3%)	208 (33.3%)	248 (35.2%)	219 (32.4%)	251 (35.9%)
≥30	426 (30.5%)	200 (32.1%)	208 (29.5%)	209 (31.0%)	212 (30.3%)
SGRQ Total Score (mean, SD)	37.7 (19.7)	44.1 (18.9)	32.37 (18.6)	44.87 (18.8)	30.81 (17.9)
CAT Total Score (mean, SD)	15.3 (7.9)	18.55 (7.6)	12.52 (7.1)	19.71 (6.8)	11.09 (6.4)

Abbreviations: BMI, body mass index; CAT, COPD Assessment Test; CMH, chronic mucus hypersecretion; FEV₁, forced expiratory volume in one second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; SD, standard deviation; SGRQ, St. George’s Respiratory Questionnaire.

Table 5 COPD Exacerbations for CMH+ and CMH− Participants Based on SGRQ and CAT Definitions

Characteristics, n (%)	Entire Cohort N=1431	SGRQ		CAT
		CMH+ N=639	CMH− N=722	CMH+ N=686	CMH− N=721
Exacerbations, 12 months prior to baseline
≥1 moderate	334 (26.1%)	175 (30.6%)	142 (21.9%)	200 (33.2%)	128 (19.5%)
≥1 severe	136 (9.6%)	62 (9.7%)	66 (9.3%)	81 (11.9%)	53 (7.4%)
≥1 severe or ≥2 moderate	265 (19.3%)	135 (22.2%)	117 (16.7%)	162 (24.7%)	99 (14.2%)
Exacerbations during 1^st year
≥1 moderate	126 (12.4%)	65 (15.4%)	54 (9.9%)	72 (15.7%)	53 (9.7%)
≥1 severe	53 (4.9%)	30 (6.6%)	20 (3.5%)	36 (7.2%)	16 (2.8%)
≥1 severe or ≥2 moderate	82 (7.7%)	44 (9.8%)	33 (5.9%)	54 (11.1%)	27 (4.8%)
Exacerbations during 2^nd year
≥1 moderate	92 (14.0%)	45 (17.2%)	42 (11.4%)	52 (18.8%)	39 (10.5%)
≥1 severe	37 (5.3%)	16 (5.8%)	17 (4.4%)	19 (6.4%)	16 (4.1%)
≥1 severe or ≥2 moderate	53 (7.7%)	26 (9.6%)	23 (6.0%)	29 (10.0%)	22 (5.7%)
Exacerbations during 3^rd year
≥1 moderate	47 (11.4%)	21 (12.5%)	25 (10.7%)	22 (12.4%)	25 (11.1%)
≥1 severe	15 (3.5%)	6 (3.5%)	6 (2.5%)	9 (4.8%)	5 (2.2%)
≥1 severe or ≥2 moderate	19 (4.5%)	8 (4.7%)	8 (3.3%)	11 (6.0%)	7 (3.0%)
Exacerbations over 1^st-3^rd years combined
≥1 moderate	210 (19.5%)	101 (22.4%)	99 (17.3%)	113 (23.3%)	96 (16.6%)
≥1 severe	94 (8.5%)	50 (10.7%)	36 (6.1%)	58 (11.4%)	32 (5.5%)
≥1 severe or ≥2 moderate	137 (12.5%)	71 (15.4%)	56 (9.6%)	83 (16.7%)	50 (8.6%)

Notes: The denominator for proportions is based on the number of participants with available data at each visit, as assessed separately for each type of exacerbation.

Abbreviations: CAT, COPD Assessment Test; CMH, chronic mucus hypersecretion; SGRQ, St. George’s Respiratory Questionnaire.

Figure 1 COPD exacerbations (percentage) among current smokers by SGRQ and CAT definitions of CMH 12 months prior to baseline and during first, second and third year of follow-up.

Abbreviations: CAT, COPD Assessment Test; CMH, chronic mucus hypersecretion; SGRQ, St. George’s Respiratory Questionnaire.

Figure 2 COPD Exacerbations (percentage) among ex-smokers by SGRQ and CAT definitions of CMH 12 months prior to baseline and during first,second and third year of follow-up.

Abbreviations: CAT, COPD Assessment Test; CMH, chronic mucus hypersecretion; SGRQ, St. George’s Respiratory Questionnaire.