Combined Pulmonary Fibrosis Emphysema: Role of Cigarette Smoking and Pulmonary Hypertension in a Rural Cohort

Figures & data

Figure 1 Development of the study groups.

Table 1 Clinical Characteristics and Outcomes in the CPFE and IPF Without Emphysema Groups

Variables % or Mean±SD	CPFE (UIP) (N=49 45%)	IPF (UIP) without Emphysema (N=60, 55%)	Total IPF (UIP) (N=109, 100%)	p-value
Historic details
Age (years)	73.90±10.42	78.20±9.46	76.27±10.10	0.026
Gender (male),%	65.3	58.3	61.5	0.457
BMI (kg/m^2)	27.12±4.77	27.17±5.29	27.15±5.05	0.958
Family history of IPF	10.6	8.8	9.6	0.748
Ever-smoker	93.9	53.3	71.6	<0.0001
Smoking pack years	49.09±29.58	15.39±14.84	35.34±29.66	<0.0001
Comorbidities
Hypertension	83.7	70	76.1	0.096
Hyperlipidemia	75.5	73.3	74.3	0.796
GERD	73.5	66.7	69.7	0.442
CAD	61.2	53.3	56.9	0.408
PH	46.9	33.3	39.4	0.148
CHF	44.9	31.7	37.6	0.156
Atrial arrhythmia	34.7	33.3	33.9	0.881
Anemia	32.7	33.3	33.0	0.940
Sleep apnea	30.6	38.3	34.9	0.400
Diabetes	30.6	30.6	30.3	0.945
Anxiety/mood disorders	28.6	28.3	28.4	0.978
CKD	28.6	21.7	24.8	0.406
Hypothyroidism	28.6	33.3	31.2	0.593
Chronic pain	20.4	21.7	21.1	0.873
PVD	16.3	6.7	11.0	0.109
CVA	14.3	25.0	20.2	0.166
DVT	12.2	13.3	12.8	0.866
Aortic aneurysm	12.2	10.2	11.0	0.710
Lung cancer	10.2	3.3	6.4	0.146
Diagnostics details
PA diameter on HRCT	30.73±3.87	29.72±4.96	30.20±4.49	0.254
TRV (cm/sec)	3.08±0.58	2.87±0.55	2.96±0.57	0.071
RVSP mmHg	49.47±23.05	42.94±15.13	45.75±19.07	0.174
PFT at the time of diagnosis
FEV1% predicted	80.80±14.66	84.30±17.89	82.86±16.57	0.313
FVC % predicted	73.76±15.65	75.83±18.79	74.98±17.43	0.699
DLCO % predicated	38.35±15.45	51.09±15.96	45.47±16.88	0.001
6MWD (meter)	242.1±114.0	255.2±136.1	249.71±126.23	0.714
Lung biopsy	12.2	15.0	13.8	0.678
Seen at tertiary or ILD center	51.0	52.5	51.9	0.875
Incident diagnosis	38.8	44.8	42.1	0.527
Prevalent diagnosis	61.2	55.2	57.9	0.527
Years since diagnosis	4.45±2.39	4.64±3.26	4.56±2.89	0.421
Symptoms duration prior to diagnosis (months)	20.41±18.96	20.76±22.12	20.60±20.55	0.943
Management details
Supplemental O2 prescribed	89.4	87.9	88.62	0.819
O2 Liter/min	3.05±2.17	2.71±1.63	2.87±1.89	0.374
Antifibrotics
Nintedanib	20.4	18.3	19.3	0.785
Pirfenidone	14.3	28.3	22.0	0.078
Lung transplant	4.1	5.0	4.6	0.820
Outcomes: Dead	38.8	26.7	32.1	0.178

Abbreviations: BMI, body mass index; CAD, coronary artery disease; CHF, congestive heart failure; CKD, chronic kidney disease; CVA, cerebrovascular accident; DL_CO, diffusion capacity for carbon monoxide; DVT, deep vein thrombosis; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; GERD, gastro-esophageal reflux disease; PA, pulmonary artery; PFT, pulmonary function test; PH, pulmonary hypertension; PVD, peripheral vascular disease; RVSP, right ventricular systolic pressure; TRV, tricuspid regurgitant velocity; 6MWD, six-minute walk distance.

Figure 2 Trend of pulmonary function tests between CPFE vs IPF without emphysema groups. Time 1: at the time of diagnosis; Time 2: latest during the disease course. There was no significant difference in the differences of decline in PFT data when measured at two different time frames of disease course (at time of diagnosis and the latest). (A) FEV₁ and FVC % predicted at time 1 and 2 between the groups (non-significant difference). (B) DL_CO % predicated at time 1 and 2 between the groups. CPFE group had significantly lower DLCO % predicted at the time 1 (38.35±15.45 vs 51.09±15.96, p = 0.001).

Table 2 Multivariate Logistic Regression Analysis: Predictors of CPFE

Factors	Odds Ratio	95% CI	p-value
Age	1.000	0.943–1.061	0.998
Ever-smoker	29.827	3.561–249.817	0.002
Pulmonary hypertension	1.718	0.501–5.888	0.389
Pulmonary artery diameter	0.986	0.868–1.121	0.832
% predicated DLCO at diagnosis	0.928	0.888–0.968	0.001

Table 3 Multivariate Logistic Regression Analysis: Predictors of Survival for Total IPF Cohort

Factors	Odds Ratio	95% CI	p-value
Body mass index (BMI)	1.134	1.005–1.207	0.038
Ever-smoker	0.839	0.303–2.324	0.735
Pulmonary hypertension	0.215	0.085–0.544	0.001
Nintedanib	2.034	0.577–7.172	0.270
Pirfenidone	3.698	1.040–13.153	0.043

Figure 3 Kaplan–Meier survival analysis of CPFE and IPF without emphysema groups. There was a trend towards reduced survival between the groups over time since their diagnosis, however not statistically different (log-rank p = 0.076). X-axis signifies years alive since diagnosis during the study time frame and Y-axis shows survival rate. The mean years since diagnosis between the groups were 4.45±2.39 vs 4.64±3.26 (p = 0.740), respectively.