The Effects of Inhaled Airway Directed Pharmacotherapy on Decline in Lung Function Parameters Among Indigenous Australian Adults With and Without Underlying Airway Disease

Figures & data

Figure 1 Study flow chart.

Table 1 Clinical Characteristics of Patients with Multiple Lung Function Tests (LFTs) Recorded (n = 115)

Clinical Parameters	First LFT	Last LFT	p-value
Age (years)^a	50.4 (48.3, 52.5)	52.2 (50.1, 54.3)	0.212
Anthropometric data and corpulence status
Height (m)^a	1.67 (1.66, 1.69)	1.67 (1.65, 1.69)	0.912
Weight (kg)^b	72 (60, 92)	74 (60, 93)	0.937
Body mass index (BMI, kg/m^2)^b	26.3 (20.8, 33)	26.6 (21.2, 32.4)	0.894
Underweight (BMI < 18.5 kg/m^2)^c	13 (11)	15 (13)	0.687
Normal weight (BMI:18.5–24.9 kg/m^2)^c	37 (32)	34 (30)	0.669
Overweight (BMI: 25.0–29.9 kg/m^2)^c	27 (23)	25 (22)	0.753
Obese (BMI ≥ 30 kg/m^2)^c	38 (33)	41 (36)	0.677
Smoking status
Never smoker^c	12 (10%)	-	-
Former smoker^c	41 (36%)	-	-
Current smoker^c	62 (54%)	-	-
Radiology Findings^
No abnormality^c	59 (51%)	-	-
Any abnormality	56 (49%)	-	-
Chronic obstructive pulmonary disease (COPD)^c	31 (28%)	-	-
Bronchiectasis^c	12 (10%)	-	-
Combined COPD + Bronchiectasis^c	13 (12%)	-	-
Airway directed inhaled pharmacotherapy
Any inhaled pharmacotherapy*^c	77 (67)	90 (78)	0.055
Short acting β2 receptor agonist^c	70 (61)	82 (72)	0.077
Short acting muscarinic antagonist^c	5 (4)	9 (8)	0.255
Long acting β2 receptor agonist^c	54 (47)	64 (56)	0.210
Long acting muscarinic antagonist^c	37 (33)	43 (38)	0.405
Inhaled corticosteroid	55 (48)	65 (57)	0.187
Other airway directed therapy
Theophylline^c	3 (3)	8 (7)	0.119
Airway clearance therapy^c	8 (7)	9 (8)	0.846
Home oxygen^c	14 (13)	15 (14)	0.884

Notes: Data were ^aMean (95% confidence interval), ^bMedian (interquartile range), ^cNumber (%). P-values were derived from equality of medians test for continuous non-parametric parameters, 2-tailed Students t-test for normally distributed parameters, or 2-tailed proportions z-test for categorical parameters. *Excluding airway clearance, home oxygen and theophylline. Two patients did not have pharmacotherapy data available, therefore in total for this section n=113. ^Includes all radiology, not just those conducted prior to the first LFT.

Table 2 Lung Function Parameters (LFPs) at First and Final Lung Function Test (LFT) (n = 115)

LFPs	First LFT	Final LFT	p-value
Forced vital capacity (FVC)
LLN (L)	3.08 (2.95, 3.21)	3.04 (2.92, 3.16)	0.673
Pre-BD (L)	2.32 (2.18, 2.46)	2.28 (2.15, 2.42)	0.674
Pre-BD (%)	60.82 (57.68, 63.96)	60.62 (57.51, 63.73)	0.926
Post-BD (L)	2.41 (2.28, 2.55)	2.39 (2.26, 2.52)	0.799
Post-BD (%)	63.35 (60.29, 66.4)	63.35 (60.34, 66.36)	0.999
BDR (%)	5.32 (3.5, 7.14)	6.62 (3.42, 9.81)	0.486
Forced expiratory volume in one second (FEV1)
LLN (L)	2.4 (2.3, 2.49)	2.36 (2.26, 2.45)	0.583
Pre-BD (L)	1.61 (1.49, 1.74)	1.56 (1.43, 1.69)	0.581
Pre-BD (%)	53.19 (49.36, 57.03)	52.14 (48.18, 56.1)	0.706
Post-BD (L)	1.71 (1.58, 1.84)	1.66 (1.53, 1.79)	0.591
Post-BD (%)	56.42 (52.51, 60.32)	55.41 (51.51, 59.3)	0.718
BDR (%)	7.29 (5.4, 9.17)	8.09 (5.96, 10.21)	0.577
FEV1/FVC
LLN (AV)	0.7 (0.69, 0.7)	0.69 (0.69, 0.7)	0.125
Pre-BD (AV)	0.68 (0.66, 0.71)	0.67 (0.64, 0.69)	0.351
Pre-BD (%)	85.61 (82.25, 88.97)	83.57 (80.21, 86.94)	0.395
Post-BD (AV)	0.7 (0.67, 0.73)	0.68 (0.65, 0.7)	0.314
Post-BD (%)	87.32 (83.79, 90.85)	85.15 (81.73, 88.57)	0.381

Notes: Data were mean (95% confidence interval). P-values were obtained via 2-tailed Students t-test.

Abbreviations: AV, absolute value; BD, bronchodilator; BDR, bronchodilator responsiveness; LLN, lower limit of normal.

Table 3 Rate of Change in Lung Function Parameters (LFPs) Values (Ml/Year or %/Year for Predicted Values) Stratified by Radiological Evidence for Chronic Airway Disease

LFPs	Total (n=115)	Without Radiological Evidence of Airway Disease (n=59)	With Radiological Evidence of Airway Disease (n=56)	p-value
Forced vital capacity (FVC)
Pre-BD (L)	−37.55 (−159.88, 92.67)	−37.64 (−92.27, 123.63)	−36.98 (−219.7, 62.68)	0.356
Pre-BD (%)	−0.53 (−4.88, 4.55)	−0.6 (−4.19, 5)	−0.48 (−5.23, 3.18)	0.549
Post-BD (L)	−21.42 (−108.68, 80.7)	−18.55 (−95.51, 90.84)	−23.69 (−132.26, 74.05)	0.650
Post-BD (%)	0.29 (−3.27, 4.23)	0.72 (−1.92, 4.17)	0 (−4.86, 5.14)	0.640
Forced expiratory volume in one second (FEV1)
Pre-BD (L)	−18.74 (−102.49, 71.44)	−12.72 (−100.94, 77.41)	−19.67 (−112.79, 41.27)	0.464
Pre-BD (%)	−0.6 (−3.49, 4.13)	−0.6 (−3.49, 4.17)	−0.7 (−3.44, 3.63)	0.511
Post-BD (L)	−22.36 (−123.65, 61.66)	−37.95 (−126.97, 80.65)	−21.29 (−110.78, 60.91)	0.724
Post-BD (%)	−0.52 (−3.95, 4)	−0.61 (−3.85, 4.17)	−0.21 (−4.22, 3.9)	0.967
Excessive FEV1 (pre-BD) decline*	65 (57)	31 (53)	34 (61)	0.377
FEV1/FVC
Pre-BD (AV)	0.00 (−0.03, 0.01)	0.00 (−0.03, 0.01)	0.00 (−0.03, 0.02)	0.867
Pre-BD (%)	0.00 (−4.21, 1.83)	0.00 (−2.87, 1.94)	−0.41 (−4.68, 1.71)	0.518
Post-BD (AV)	−0.01 (−0.03, 0.01)	−0.01 (−0.02, 0.01)	−0.01 (−0.03, 0.02)	0.840
Post-BD (%)	−0.46 (−3.77, 1.81)	−0.46 (−3, 1.63)	−0.43 (−4.66, 1.88)	0.887

Notes: Data were median (IQR). P-values were obtained via Wilcoxon rank-sum test between patients with/without radiological evidence of airway disease for continuous parameters and chi-squared test for categorical parameters. *(Baseline predicted FEV₁ – current predicted FEV₁) + (0.15 x Baseline absolute FEV₁).

Abbreviations: AV, absolute value; BD, bronchodilator.

Table 4 Rate of Change in Lung Function Parameters Values (Ml/Year for Predicted Values) Between Levels of Smoking Recorded (Note Smoking Status Adjudged as the Highest Smoking Level Reported Through the Study Period)

LFPs	Non-Smoker n=12	Former Smoker n=41	Current Smoker n=62	p-value
Forced vital capacity (FVC)
Pre-BD (mL)	−50.14 (−245.93, 50.03)	−44.83 (−225.7, 47.3)	−21.46 (−126.45, 170.76)	0.553
Pre-BD (%)	−1.44 (−4.87, 1.89)	−1.81 (−5.19, 1.62)	1.51 (−3.17, 7.76)	0.114
Post-BD (mL)	9.24 (−214.62, 33.33)	−25.61 (−103.14, 60.33)	−11.3 (−108.7, 120.12)	0.739
Post-BD (%)	−0.15 (−2.73, 2.01)	0 (−4.37, 2.06)	1.27 (−2.61, 5.96)	0.263
Forced expiratory volume in one second (FEV1)
Pre-BD (mL)	−50.06 (−277.39, 26.62)	−12.72 (−98.1, 71.44)	−17.26 (−101.05, 78.55)	0.837
Pre-BD (%)	−1.77 (−7.76, 1.52)	−1.65 (−4.24, 2.63)	1.2 (−2.36, 4.4)	0.196
Post-BD (mL)	−34.52 (−173.94, 21.69)	−43.62 (−126.97, 52.31)	−12.86 (−99.48, 191.6)	0.704
Post-BD (%)	−0.87 (−5.2, 3.96)	−1.83 (−4.84, 2.72)	0.92 (−2.92, 6.25)	0.178
Excessive FEV1 (pre-BD) decline*	8 (67)	25 (61)	32 (52)	0.486
FEV1/FVC
Pre-BD (AV)	0 (−0.03, 0.01)	0 (−0.02, 0.01)	−0.01 (−0.03, 0.01)	0.921
Pre-BD (%)	−1.22 (−4.84, 0.18)	0 (−2.47, 2.02)	−0.38 (−4.21, 1.83)	0.828
Post-BD (AV)	−0.01 (−0.02, 0.03)	−0.01 (−0.02, 0.01)	−0.01 (−0.03, 0.02)	0.796
Post-BD (%)	−0.95 (−3.26, 0.18)	−0.32 (−3, 1.81)	−0.49 (−4.23, 2.52)	0.981

Notes: Data were median (IQR). P-values were obtained via univariate quantile regression for continuous parameters and chi-squared test for categorical parameters. *(Baseline predicted FEV₁ – current predicted FEV₁) + (0.15 × baseline absolute FEV₁).

Abbreviations: AV, absolute value; BD, bronchodilator; LFPs, lung function parameters.

Table 5 Rate of Change in Lung Function Parameters Values (ml/Year for Predicted Values) Between Inhaled Pharmacotherapy Use (Note Pharmacotherapy Level Adjudged from What Was Reported at the Final Lung Function Test)

Univariate	No Medication (n=25)	SA/LA BA/MA (n=25)	SA/LA BA/MA + ICS (n=63)	p-value
Forced vital capacity (FVC)
Pre-BD (L)	−22.5 (−79.73, 207.02)	17.77 (−91.48, 113.8)	−52.66 (−197.52, 60.36)	0.074
Pre-BD (%)	−0.82 (−5.19, 4.55)	2.7 (−3.57, 7.76)	−0.6 (−4.37, 2.01)	0.164
Post-BD (L)	32.68 (−64.91, 112.05)	10.57 (−77.6, 80.38)	−50.47 (−141.14, 64.71)	0.064
Post-BD (%)	0.72 (−4.2, 4.17)	2.79 (−1.01, 6.04)	0 (−3.52, 2.43)	0.199
Forced expiratory volume in one second (FEV1)
Pre-BD (L)	−5.76 (−63.19, 67.34)	15.46 (−73.5, 74.62)	−48.64 (−110.18, 62.5)	0.022*
Pre-BD (%)	−0.69 (−6.09, 4.17)	2 (−2.27, 4.4)	−0.82 (−3.4, 1.89)	0.027*
Post-BD (L)	−27.53 (−116.19, 142.87)	21.59 (−45.02, 56.66)	−37.95 (−123.65, 60.17)	0.593
Post-BD (%)	−0.69 (−4.35, 5.98)	2.65 (−2, 4.61)	−0.81 (−4.4, 2.13)	0.135
Excessive FEV1 (pre-BD) decline^	13 (52)	11 (44)	40 (64)	0.218
FEV1/FVC
Pre-BD (AV)	0 (−0.03, 0.01)	0 (−0.02, 0.01)	0 (−0.04, 0.01)	0.880
Pre-BD (%)	0 (−2.76, 1.82)	−0.66 (−3.03, 2.02)	0 (−4.85, 1.83)	0.826
Post-BD (AV)	−0.01 (−0.03, 0)	0 (−0.02, 0)	−0.01 (−0.03, 0.02)	0.645
Post-BD (%)	−0.35 (−2.73, 3.49)	−0.53 (−3, 0.98)	0 (−4.82, 1.81)	0.988

Notes: Data were median (IQR). P-values were obtained via univariate quantile regression for continuous parameters and chi-squared test for categorical parameters. ^(Baseline predicted FEV₁ – current predicted FEV₁) + (0.15 × baseline absolute FEV₁). *denotes statistically significant difference (p<0.05).

Abbreviations: AV, absolute value; BD, bronchodilator; ICS, inhaled corticosteroids; SA/LA BA/MA, short acting/long acting β₂ receptor agonist/muscarinic antagonist’.

Table 6 Clinical Characteristics of Patients with Multiple Lung Function Tests (LFTs) Recorded Stratified by Level of Pharmacotherapy Reported

Clinical Parameters	No Medication (n=25)	SA/LA BA/MA (n=25)	SA/LA BA/MA + ICS (n=63)	p-value
Age (years)^a	45.22 (40.12, 50.32)	56.73 (52.44, 61.02)	53.13 (50.52, 55.74)	0.018*
Anthropometric data and corpulence status
Height (m)^a	1.68 (1.65, 1.72)	1.68 (1.64, 1.72)	1.66 (1.64, 1.68)	0.134
Weight (kg)^b	94 (75, 105)	71 (58, 91)	69 (60, 84)	<0.001*
Body mass index (BMI, kg/m^2)^b	32.61 (25.43, 37.81)	23.61 (20.44, 32.41)	25.24 (21.56, 30.39)	0.042*
Underweight (BMI < 18.5 kg/m^2)^c	3 (12)	3 (12)	9 (14)	0.939
Normal weight (BMI:18.5–24.9 kg/m^2)^c	3 (12)	10 (40)	21 (33)	0.068
Overweight (BMI: 25.0–29.9 kg/m^2)^c	3 (12)	5 (20)	16 (25)	0.377
Obese (BMI ≥ 30 kg/m^2) ^c	16 (64)	7 (28)	17 (27)	0.003*
Smoking status
Never smoker^c	3 (12)	0 (0)	8 (13)	0.176
Former smoker^c	10 (40)	8 (32)	25 (40)	0.779
Current smoker^c	12 (48)	17 (68)	30 (48)	0.201
Pack Years^b	12.5 (5.3, 45)	17.5 (5, 55.6)	25 (8.3, 39)	0.230
Radiology Findings
No abnormality^c	20 (80)	13 (52)	24 (38)	0.002*
Any abnormality^c	5 (20)	12 (48)	39 (62)	0.002*
Chronic obstructive pulmonary disease (COPD)^c	2 (8)	10 (40)	32 (51)	0.001*
Bronchiectasis^c	3 (12)	5 (20)	17 (27)	0.299
Combined COPD + Bronchiectasis^c	0 (0)	3 (12)	10 (16)	0.109
Mortality
Deceased^c	0 (0)	1 (4)	12 (19)	0.016*
Age deceased (years)^a		52.53	53.17 (45.67, 60.66)	0.959

Notes: Data were mean (95% confidence interval). P-values were obtained via (a) univariate linear regression for parametrically distributed parameters, (b) univariate quantile regression for non-parametrically distributed parameters, and (c) chi-squared test for categorical parameters. *Statistically significant (p-value <0.05).

Abbreviations: ICS, inhaled corticosteroids; SA/LA BA/MA, short acting/long acting β₂ receptor agonist/muscarinic antagonist’.

Figure 2 Coefficient plot showing univariate linear regression effects (Beta [95% confidence interval]) for normally distributed and quantile linear regression effects (Beta [95% confidence interval]) for non-parametrically distributed clinical characteristics by reported levels of pharmacotherapy usage against no pharmacotherapy.

Abbreviations: BMI, body mass index; ICS, inhaled corticosteroids.

Figure 3 Coefficient plot showing univariate logistic regression effects (Odds ratio [95% confidence interval]) by reported levels of pharmacotherapy usage against no pharmacotherapy. Note that non-smoker and combined chronic obstructive pulmonary disease (COPD) + bronchiectasis are omitted due to low numbers.

Abbreviation: ICS, inhaled corticosteroids.