Transition from Restrictive to Obstructive Lung Function Impairment During Treatment and Follow-Up of Active Tuberculosis

Figures & data

Table 1 Baseline Demographic and Spirometric Characteristics

Population Characteristics	Number (% of Patients)
(n=43)
Male – n (%)	16 (37.2%)
Age – years, median (range)	26 (20 to 65)
Race
African – n (%)	10 (23.3%)
Mixed race – n (%)	33 (76.7%)
Smoking Status
Never smokers – n (%)	12 (27.9%)
Former-smokers – n (%)	11 (25.6%)
Current smokers – n (%)	20 (46.5%)
Pack years for ever smokers – median (IQR)	3.0 (1.4–8.1)
HIV positive – n (%)	2 (4.7%)
Baseline Spirometry (Post-Bd)
	Median (IQR)
FEV1 (L)	1.97 (1.50 to 2.76)
FEV1 (%pred.)	0.59 (0.50 to 0.77)
FVC (L)	2.49 (1.90 to 3.02)
FVC (%pred.)	0.63 (0.54 to 0.73)
FEV1/FVC (%)	81.9 (75.2 to 88.1)
FEV1/FVC< LLN	9 (20.9%)
FEV1/FVC< 0.70	5 (11.6%)

Abbreviations: SD, standard deviation; FEV1, forced vital capacity in 1 sec; FVC, forced vital capacity; %pred., percentage of predicted value; L, litres; AFO, air flow obstruction; LLN, lower limit of normal.

Figure 1 Recruitment and exclusion of subjects.

Table 2 Lung Physiology Data at 2, 6 (Treatment Completion) and 18 Months (One Year After Treatment Completion)

n=43	Baseline		2 Months		6 Months			18 Months
	Median	(IQR)	Median	(IQR)	Median	(IQR)		Median	(IQR)
FEV1 (L)	1.97	(1.50–2.76)	2.27	(1.68 −2.89)	2.39	(1.80–2.92)		2.52	(1.95–3.04)
FEV1 (%pred.)	0.59	(0.50–0.77)	0.73	(0.55–0.86)	0.75	(0.59–0.87)		0.79	(0.64–0.89)
FVC (L)	2.49	(1.90–3.02)	2.82	(2.22–3.44)	2.88	(2.30–3.54)		3.05	(2.54–3.59)
FVC (%pred.)	0.63	(0.54–0.73)	0.74	(0.57–0.84)	0.77	(0.62–0.87)		0.81	(0.66–0.88)
FEV1/FVC (%)	81.9	(75.2–88.1)	81.6	(76.2–89.0)	81.5	(75.3–88.2)		87.6	(75.4–89.9)
TLC (%pred.)	–	–	85.84	(72.40–93.76)	86.76	(78.17–100.12)		97.97	(83.96–110.69)
IC (%pred.)	–	–	82.05	(68.78–97.72)	83.67	(64.01–106.23)		88.16	(70.00–112.21)
FRC (%pred.)	–	–	89.53	(67.39–106.47)	97.15	(78.63–116.88)		105.43	(86.00–128.60)
RV (%pred.)	–	–	132.62	(97.73–156.62)	132.78	(102.01–164.17)		158.29	(111.66–210.65)
RV/TLC (%)	–	–	38.3	(32.5–46.8)	37.2	(32.5–47.9)		40.9	(35.4–50.0)
IC/TLC ratio	–	–	46.9	(41.3–53.3)	45.4	(35.1–50.8)		42.5	(36.7–46.5)
DLco (%pred.)^a	–	–	66.98	(51.42–76.46)	61.68	(52.29–73.48)		65.31	(52.33–77.05)
DLco/VA (%pred.)	–	–	92.13	(83.73–103.02)	89.44	(80.32–101.20)		90.99	(75.67–100.35)
Six-minute walk distance (m)	510	(465–545)	510	(480–555)	529	(480–570)		520	(480–600)
SGRQ – Total Score
Mean (SD)	-	-	-	-	6.7		(11.0)	2.9	(9.9)
Median (IQR)	-	-	-	-	1.0		(0.00–12.3)	0.00	(0.00–0.4)
SGRQ – Activity Score
Mean (SD)	-	-	-	-	14.0		(25.9)	3.5	(15.5)
Median (IQR)	-	-			0.0		(0.0–24.4)	0.0	(0.0–0.0)

Notes: Plethysmography and diffusing capacity were not performed prior to 2 months due to risk to staff. St. George’s Respiratory Questionnaire (SGRQ) was only performed from 6 months, as it is only validated for chronic symptoms. ^aFor diffusing capacity measurements, n=42.

Abbreviations: IQR, interquartile range; SD, standard deviation; FEV1, forced vital capacity in 1 sec; FVC, forced vital capacity; TLC, total lung capacity; IC, inspiratory capacity; FRC, functional residual capacity; RV, residual volume; DLco, diffusing capacity for carbon monoxide; VA, alveolar volume; L, liters; %pred., percentage of predicted; m, meters; SGRQ, St. George’s Respiratory Questionnaire.

Figure 2 Median lung volumes measured by plethysmography at 2 (Visit 2), 6 (Visit 3, treatment completion) and 18 months (Visit 5).

Abbreviations: TLC, total lung capacity; IC, inspiratory capacity; FRC, functional residual capacity; RV, residual volume.

Figure 3 Venn diagram presenting in approximate proportions the number of patients with single and combinations of lung function abnormalities one year after completion of TB treatment (Visit 5): Airflow obstruction, gas trapping, restriction, and low diffusing capacity. Airflow obstruction was defined using the FEV₁/FVC < lower limit of normal definition; restriction was defined as total lung capacity (TLC) less than 80% predicted; gas trapping on plethysmography was defined as a residual volume (RV) to TLC ratio (RV/TLC) of greater than 45%; and a low DLco (corrected for haemoglobin) was defined as values of less than 80% predicted.

Table 3 Quantitative Computed Tomography Values for Subjects with Scans Performed at 2, 6 (Treatment Completion) and 18 Months (One Year After Treatment Completion)

n=20	2 Months		6 Months		18 Months		Change 2 to 6 Months	Change 6 to 18 Months	Change 2 to 18 Months
	Median	(IQR)	Median	(IQR)	Median	(IQR)	P-value^c	P-value^c	P-value^c
TLC (L)	3.91	(3.14–4.44)	4.01	(3.39–4.57)	4.06	(3.46–4.69)	0.01	0.99	0.16
RV (L)	1.89	(1.58–2.36)	1.79	(1.56–2.19)	1.96^a	(1.65–2.19)	0.41	0.86	0.77
LAA (%^b)	9.07%	(4.57–11.04)	8.76%	(6.78–11.63)	9.84%	(7.75–14.45)	0.20	0.11	0.02
GTS (%^b)	5.26%	(2.79–9.16)	6.85%	(4.23–10.98)	7.13%^a	(4.79–15.87)	0.19	0.04	0.02
QLF (%)	2.15%	(1.31–3.41)	1.14%	(0.72–1.67)	0.76%	(0.57–1.55)	<0.01	0.11	<0.01
QLF (mL)	84.67	(63.50–139.12)	38.30	(31.51–69.51)	30.48	(21.85–72.13)	<0.01	0.07	<0.01

Notes: ^an=19. ^bPercentage of total lung volume. ^cP-value for paired Wilcoxon test.

Abbreviations: TLC, total lung capacity; RV, residual volume; LAA, low-attenuation areas on inspiratory scan (ie,<-950HU, emphysema score); GTS, gas-trapping score on expiratory scan (ie, <-856HU); QLF, quantity of lung fibrosis; L, litres; mL, milliliters.

Figure 4 Inspiratory and expiratory, axial and coronal computed tomography images for a 20-year-old female, after 2 months of tuberculosis treatment (Visit 2) (A), and 1 year after treatment completion (Visit 5) (B). Resolution of infiltrates of tuberculosis and improvement in inspiratory lung volumes was found. However, areas of gas trapping can be seen on the Visit 5 expiratory scan which were not present at 2 months, and are particularly prominent in regions where infiltrates of tuberculosis have resolved.