Acupressure for Cough in Lung Cancer Survivors

Lung cancer survivors often exhibit multiple symptoms, among which cough and its co-occurring symptoms have been identified as a group of prevalent and persistent symptoms that substantially impact their quality of life and overall survival. Research has identified cough as the sentinel symptom of the respiratory symptom cluster in lung cancer patients, underscoring the critical need for effective management strategies. This randomized controlled trial aims to evaluate the effect of a safe and self-administerable acupressure intervention on alleviating cough, reducing the dyspnea-cough-fatigue symptom cluster, and improving symptom burden, functional capacity, and quality of life in this patient population.

• acupressure (Behavioral): Participants will perform acupressure for 8 weeks and keep practice records in a diary log. Trainers will follow up with the participants twice weekly via phone or face-to-face to assess and reinforce their practice and address acupressure-related questions.
• Education (Other): Participants will receive an educational booklet in the first week after the baseline assessment and complete evaluations concurrently with the experimental group. Upon study completion, they will be offered a place on a waitlist for the same acupressure intervention provided to the experimental group.

Primary outcomes

• Cough [Pre-intervention (T0, baseline); Early intervention (T1, 1 week after T0); Post-intervention (T2, 8 weeks after T0); Follow-up (T3, 16 weeks after T0)]: The cough will be evaluated using the Cough Evaluation Test (CET). The 5-item instrument assesses cough under physical, psychological and social domains, with each item graded on a five-point scale, with a higher total score indicating a greater level of symptom and an MCID of 2 points.

Secondary outcomes

• Cough-related quality of life [Pre-intervention (T0, baseline); Early intervention (T1, 1 week after T0); Post-intervention (T2, 8 weeks after T0); Follow-up (T3, 16 weeks after T0)]: The Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC) will be used to assess cough-related quality of life. The widely adopted questionnaire has established satisfactory internal consistency (with Cronbach's α between 0.74 and 0.90) and test-retest reliability (with intraclass correlation coefficients between 0.89 and 0.95). The 19-item LCQ-MC has an MCID of 3.0 points. A lower total score indicates a greater level of symptom severity and poorer cough-related quality of life.
• Dyspnea-cough-fatigue symptom cluster [Pre-intervention (T0, baseline); Early intervention (T1, 1 week after T0); Post-intervention (T2, 8 weeks after T0); Follow-up (T3, 16 weeks after T0)]: The dyspnea-cough-fatigue symptom cluster will be assessed in terms of the occurrence and severity. The presence of the symptom cluster is defined as having all three symptoms. Severity of the dyspnea-cough-fatigue symptom cluster will be quantified using the average score of all three items (dyspnea, cough, and fatigue) from the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC).
• Dyspnea [Pre-intervention (T0, baseline); Early intervention (T1, 1 week after T0); Post-intervention (T2, 8 weeks after T0); Follow-up (T3, 16 weeks after T0)]: Dyspnea will be measured using Dyspnea-12 (D-12). The 12-item instrument consists of two subscales (physical and affective), with each item graded on a 4-point scale from 0 (no dyspnea) to 3 (severe dyspnea).
• Fatigue [Pre-intervention (T0, baseline); Early intervention (T1, 1 week after T0); Post-intervention (T2, 8 weeks after T0); Follow-up (T3, 16 weeks after T0)]: The 9-item Brief Fatigue Inventory (BFI) will be used to measure fatigue levels. The instrument has two dimensions - severity and interference, with a higher total score indicating a greater symptom burden.
• Symptom burden [Pre-intervention (T0, baseline); Early intervention (T1, 1 week after T0); Post-intervention (T2, 8 weeks after T0); Follow-up (T3, 16 weeks after T0)]: The symptom burden of the participants will be measured using the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC), which consists of 16 symptom items and 6 interference items.
• Functional capacity [Pre-intervention (T0, baseline); Post-intervention (T2, 8 weeks after T0); Follow-up (T3, 16 weeks after T0)]: Functional capacity will be assessed using the 6-minute Walking Test (6MWT), a valid and widely used test among patients with respiratory diseases.
• Health-related quality of life [Pre-intervention (T0, baseline); Early intervention (T1, 1 week after T0); Post-intervention (T2, 8 weeks after T0); Follow-up (T3, 16 weeks after T0)]: Health-related quality of life will be measured with the 36-item Functional Assessment of Cancer Therapy-Lung (FACT-L) under five dimensions: physical, emotional, social, functional well-being, and LC-specific symptoms.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* be at least 18 years of age;
* have a diagnosis of LC at any stage and of any pathological type;
* have a cough symptom rating ≥3 on a 0 to 10 numeric rating scale within 7 days preceding enrollment;
* can perform acupressure independently in daily activities;
* be able to read Chinese and communicate in Cantonese or Mandarin;
* be able to provide informed consent.

Exclusion Criteria:

* have unstable chronic diseases other than LC;
* have received acupressure or acupuncture within the three months preceding study enrollment;
* have serious illnesses or other conditions that prevent the participants from following the intervention protocols;
* have a life expectancy of less than 3 months;
* Be currently participating in other research programs that may affect the outcomes under investigation.

• Results publication: Luo Y, Luo J, Su Q, Yang Z, Miao J, Zhang L. Exploring Central and Bridge Symptoms in Patients with Lung Cancer: A Network Analysis. Semin Oncol Nurs. 2024 Jun;40(3):151651. doi: 10.1016/j.soncn.2024.151651. Epub 2024 May 3. PMID 38704342
• Results publication: Zhou X, Lei C, Wei X, Dai W, Xu W, Ao Y, Li X, Qiao G, Shi Q. Patient's experiences of coughing after lung cancer surgery: A multicenter qualitative study. Cancer Med. 2024 Jan;13(2):e6993. doi: 10.1002/cam4.6993. PMID 38348918
• Results publication: Yang X, Bai J, Zhang J, Wang Y, Zhao H, Zhu X. Symptom clusters and their impacts on the quality of life of patients with lung cancer receiving immunotherapy: A cross-sectional study. J Clin Nurs. 2025 May;34(5):1725-1740. doi: 10.1111/jocn.17321. Epub 2024 Jun 17. PMID 38886988
• Results publication: Takemura N, Yorke J. Respiratory symptom cluster in people with lung cancer. Curr Opin Support Palliat Care. 2025 Jun 1;19(2):71-76. doi: 10.1097/SPC.0000000000000754. Epub 2025 Mar 19. PMID 40265563
• Results publication: Molassiotis A, Vu DV, Ching SSY. The Effectiveness of Qigong in Managing a Cluster of Symptoms (Breathlessness-Fatigue-Anxiety) in Patients with Lung Cancer: A Randomized Controlled Trial. Integr Cancer Ther. 2021 Jan-Dec;20:15347354211008253. doi: 10.1177/15347354211008253. PMID 33847150
• Results publication: Yorke J, Johnson MJ, Punnett G, Smith J, Blackhall F, Lloyd Williams M, Mackereth P, Haines J, Ryder D, Krishan A, Davies L, Khan A, Molassiotis A. Respiratory distress symptom intervention for non-pharmacological management of the lung cancer breathlessness-cough-fatigue symptom cluster: randomised controlled trial. BMJ Support Palliat Care. 2024 Jan 8;13(e3):e1181-e1190. doi: 10.1136/spcare-2022-003924. PMID 36283797
• Results publication: Karlsson K, Olsson C, Erlandsson A, Ahlberg KM, Larsson M. Exploring Symptom Clusters and Their Measurements in Patients With Lung Cancer: A Scoping Review for Practice and Research. Oncol Nurs Forum. 2023 Oct 19;50(6):783-815. doi: 10.1188/23.ONF.783-815. PMID 37874760
• Results publication: Cheville AL, Novotny PJ, Sloan JA, Basford JR, Wampfler JA, Garces YI, Jatoi A, Yang P. The value of a symptom cluster of fatigue, dyspnea, and cough in predicting clinical outcomes in lung cancer survivors. J Pain Symptom Manage. 2011 Aug;42(2):213-21. doi: 10.1016/j.jpainsymman.2010.11.005. Epub 2011 Mar 12. PMID 21398089
• Results publication: Molassiotis A, Lowe M, Blackhall F, Lorigan P. A qualitative exploration of a respiratory distress symptom cluster in lung cancer: cough, breathlessness and fatigue. Lung Cancer. 2011 Jan;71(1):94-102. doi: 10.1016/j.lungcan.2010.04.002. Epub 2010 May 2. PMID 20439127
• Results publication: Li Y, Wang Q, Liu C, Hu X. Symptom clusters and their impact on quality of life among Chinese patients with lung cancer: A cross-sectional study. Eur J Oncol Nurs. 2023 Dec;67:102465. doi: 10.1016/j.ejon.2023.102465. Epub 2023 Nov 7. PMID 37956567
• Results publication: Chen K, Yang D, Li F, Gao L, Tian Y, Xu B, Xu X, Xu Q, Cao J. Changes in the symptom clusters of elderly patients with lung cancer over the course of postoperative rehabilitation and their correlation with frailty and quality of life: A longitudinal study. Eur J Oncol Nurs. 2023 Dec;67:102388. doi: 10.1016/j.ejon.2023.102388. Epub 2023 Jul 24. PMID 37948789

• Denise Shuk Ting Cheung, PhD, Study director, The University of Hong Kong