Table 3.
Quantitative and mixed-methods studies in mixed ILD
| Author year | Cough category | Study design | Arm | Disease severity (FVC % pred.) | Cough severity measures | HRQoL/impact measures | Group comparisons | Burden of cough | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Interventional trials | |||||||||||
| Bassi 2021 | Broader includes | Open-label RCT | Fibrosing ILD: 50 | 69.6 (2.15) | VAS: 52.3 (32.8) | MRQr: 11.6 (6.0) | VAS cough worsened both in intervention and usual care group (p-value group effect: 0.88) | Depression (CES-D) and dyspnoea (MRQr) were improved by the intervention, but cough was not | |||
| CES-D: 13.8 (8.1) | |||||||||||
| Sato 2021 | Chronic cough | Pre-post intervention study | CTD-ILD, IIP: 11 | 77.8 (63.9–88.1) | VAS: 63 (35–79) | LCQ (acute): 13.4 (11.0–14.9) | – | Correlation not presented | |||
| Observational studies | |||||||||||
| Cheng 2017 | Chronic cough | Cohort study | IPF: 77 | 73.2 (18.1) | VAS: no baseline | SGRQ: no baseline | Cough was most prevalent in IPF and most productive in CHP | Cough severity was an independent predictor of total SGRQ after adjustments in SSc-ILD and IPF but not CHP | |||
| CHP: 32 | 67.0 (19.8) | ||||||||||
| SSc-ILD: 67 | 74.6 (22.0) | ||||||||||
| Lan 2021 | Chronic cough | Cross-sectional study | ILD with cough: 118 | 74.6 (18.7) | VAS: 41.8 (25.9) |
LCQ: 14.9 (4.3) Physical: 5.1 (1.5) Physiological: 5.3 (1.7) Social: 4.5 (1.5) |
Prevalence of cough was highest in IPF, NSIP and sarcoidosis patients (> 70%) | Cough ranked as worse ILD symptom in over a third of patients | |||
| ILD with no cough: 46 | 87.0 (15.9) | ||||||||||
| Minuk 2023 | Broader includes | Cohort study | ILD: 102 | 46 (12) | ESAS cough score: 7 (IQR 4–9) | Cough was worse in patients with ILD at baseline and they had lower drowsiness scores compared with patients with COPD | – | ||||
| COPD: 24 | NR | ESAS cough score: 4 (IQR 1–7) | |||||||||
| Sato 2019 | Minority cough | Cross-sectional study | IIPs (incl IPF: 70 | 85.2 (74.2–97.3) | VAS: 31 (17–55) | LCQ: 19.3 (IQR:17.5–20.4) | Patients with the IIPs had the greatest intensity of cough but not frequency of cough | Patients in whom cough frequency was predominant had a greater impairment of health status relative to other patients. Significant correlation between total LCQ scores and intensity and frequency of cough were −0.675 and −0.762, respectively | |||
| CTD-ILD: 49 | 93.6 (80.2–106.1) | VAS: 24 (8–46) | LCQ: 18.7 (IQR:15.4–20.5) | ||||||||
| CHP: 10 | 73.6 (68.8–93.3) | VAS: 18 (6–20) | LCQ: 19.6 (IQR:18.3–20.6) | ||||||||
| Veit 2023 | Majority cough | Prospective cohort | Non-IPF ILD: 22 | 63.4 (23.5) | VAS: 2.5 (2.4)* | SGRQ: 48.9 (20) | Patients with IPF not only had a higher burden of cough at the beginning of the study, but also experienced a greater increase in cough over time than those with non-IPF ILD. Patients with IPF had significantly more limitations in terms of KBILD values compared to those with non-IPF ILD; p = 0.022). SGRQ did not show significant differences between IPF and non-IPF ILD; p = 0.193) | For KBILD, but not SGRQ, there was a significant inverse correlation with VAS cough | |||
| KBILD: 53.1 (12.1) | |||||||||||
| IPF: 13 | 68.5 (18.7) | VAS: 4.6 (2.7)* | SGRQ: 51.1 (9.8) | ||||||||
| KBILD: 48.2 (2.6) | |||||||||||
| Yuan 2020 | Broader includes | Cross sectional, longitudinal and prospective study | IIP: 139 | 86.9 (22.2) | – |
LCQ: 16.7 (3.7) Physical: 5.4 (1.3) Physiological: 5.5 (1.3) Social: 5.8 (1.3) |
Average cough scores were comparable between IIP and CTD-ILD, HRQoL was lower in CTD-ILD | Cough impact correlates with quality of life at baseline and over time | |||
| SGRQ: 32.9 (19.1) | |||||||||||
|
HADS-A: 5.0 (3.0–7.0) HADS-D: 5.0 (1.0–7.0) | |||||||||||
|
SF-36 Physical: 37.2 (12.0) Mental: 48.3 (11.6) | |||||||||||
| CTD-ILD: 30 | 74.4 (19.1) | – |
LCQ: 16.3 (3.7) Physical: 5.3 (1.3) Physiological: 5.4 (1.3) Social: 5.7 (1.3) |
||||||||
| SGRQ: 43.3 (20.6) | |||||||||||
|
HADS-A: 6.0 (3.0–9.0) HADS-D: 5.5 (2.7–9.2) | |||||||||||
|
SF-36 Physical: 31.1 (14.2) Mental: 45.6 (11.1) | |||||||||||
| Validation studies | |||||||||||
| Nagata 2012 | Broader includes | Validation study | ILD (excl. IPF): 55 | 72.7 (17.3) | – | LCQ: 97.5 (39–133) | – | Cough strongly contributes to quality of life | |||
| SGRQ: 43.2 (0.0–83.9) | |||||||||||
| CAT: 13 (1–33) | |||||||||||
|
HADS-A: 4 (0–15) HADS-D: 4 (0–13) | |||||||||||
| Pan 2019 | Broader includes | Validation study | IPF: 20 | NR | – | SGRQ:78.65 (10.84) | Cough domains were significantly worse in IPF than non-IPF ILD,p < 0.001) | Many aspects of HRQoL were impaired in IPF according to the cATAQ-IPF score | |||
|
cATAQ-IPF total: 287.90 (22.56) Cough: 24.70 (4.66) | |||||||||||
| Non-IPF ILD: 72 | NR | – | SGRQ: 57.47 (21.81) | ||||||||
|
cATAQ-IPF total: 250.74 (47.39) Cough: 17.58 (7.80) | |||||||||||
| Yates 2018 | Broader includes | Validation study | IPF: 30 | NR | VAS: 38 (20) | NR | No significant difference in cough severity at baseline or interval change between IPF and non IPF subgroups | VAS cough did not correlate with KBILD | |||
| Non-IPF ILD: 67 | NR | VAS: 44 (29) | NR | ||||||||
| Total initial cohort: 64 | 82.5 (18.8) | VAS: 43 (26) | KBILD: 62.6 (21.4) | ||||||||
| Total validation cohort: 31 | 88.9 (20.1) | VAS: 41 (30) | KBILD: 62.5 (22.7) | ||||||||
| Kirsten 2022 | Broader includes | Validation study | IPF and NSIP: 200 | NR | – |
SGRQ: 38.8 QPF-scale total: 97.11 QPF-scale cough: 4.23 |
– | Cough scale included in the quality-of-life tool | |||
| Mixed methods studies | |||||||||||
| Paixão 2023 | Broader includes | Mixed methods | ILD and IPF: 10 | 77.1 (4.4) | – |
CASA-Q cough symptoms: 83.3 (75–100) CASA-Q cough impact: 100 (78.1–100) SGRQ total: 48.6 (19.4) CAT: 14.9 (8.4) HADS-A: 5.3 (5) HADS-D: 7.1 (4.5) |
Cough symptoms improved after 12 weeks of intervention | Correlation with quality of life not presented | |||
| Economic study (observational design) | |||||||||||
| Algamdi 2019 | Minority cough | Cross-sectional study | Fibrotic ILD employed: 148 | 74.8 (20) | VAS: no baseline |
Estimated annual costs of productivity loss: CAN$11,610 per patient Hours lost, mean (SE): 7.8 (0.9) |
The costs of productivity loss were comparable between employed male and female patients and between IPF and non-IPF patients ($11,737 vs $11,535). | Cough was an independent predictor of workplace productivity loss. | |||
| Fibrotic ILD unemployed: 502 | 73.3 (20.5) | ||||||||||
Mean (SD) or median (range or IQR)
*Reported on alternative 0–10 cm scale
** Reported on alternative 100-point scale
CAN, Canadian dollar; CAT, COPD Assessment Test; cATAQ-IPF, Chinese version of the A Tool To Assess Quality of Life in Idiopathic Pulmonary Fibrosis; CES-D, Center for Epidemiologic Studies Depression Scale; CHP, chronic hypersensitivity pneumonitis; CTD-ILD, connective tissue disease-associated interstitial lung disease, FVC, forced vital capacity; HADS-A, Hospital Anxiety and Depression Scale Anxiety score; HADS-D, Hospital Anxiety and Depression Scale Depression score; HRQoL, health-related quality of life; IIP, idiopathic interstitial pneumonia; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; IQR, interquartile range; KBILD, King’s Brief Interstitial Lung Disease; LCM Leicester Cough Monitor; LCQ, Leicester Cough Questionnaire; MRQr, Maugeri Respiratory Questionnaire; NR, not reported; NSIP, non-specific interstitial pneumonia, PF-ILD, progressive fibrosing interstitial lung disease; QPF, Quality of life in patients with idiopathic pulmonary fibrosis tool; RA, rheumatoid arthritis; RCT, randomised controlled trial; SE, standard error; SGRQ, St. George’s Respiratory Questionnaire; SSc, systemic sclerosis; VAS, visual analogue scale