Review of Respiratory Medicine - Volumen 24, Número 2 - June 2024

Special Article

Series on Dyspnea. Part 5. Subjective Experience of Breathlessness: total dyspnea, refractory dyspnea, chronic dyspnea syndrome, terminal dyspnea

Series en Disnea. Parte 5. Experiencia subjetiva de la dificultad para respirar: Disnea total, disnea refractaria, síndrome de disnea crónica, disnea terminal

ABSTRACT

The concept of breathlessness emphasizes the multidimensional subjective nature of dyspnea with physical, psychological, social, spiritual, and existential components. “Total dyspnea” advocates a comprehensive, patient-oriented approach beyond the disease. The term “refractory dyspnea” should be avoided; it implies a certain therapeutic nihilism. For this reason, the term “chronic dyspnea syndrome” was coined to recognize treatment possibilities and raise awareness among patients, physicians, healthcare teams, and researchers. People with advanced respiratory disease and severe chronic dyspnea (and people who are close to them) have a poor quality of life. The Breathing-Thinking- Functioning clinical-conceptual model includes the three predominant cognitive and behavioral reactions that worsen and maintain the symptom by causing vicious circles. Various instruments are available for the comprehensive assessment of dyspnea that take into account the sensory-perceptual experience, affective distress, and the impact or burden of the symptoms. Breathlessness during the last weeks or days of life can be called “terminal dyspnea.” It is a common symptom and one of the most distressing in the latest phase of life of patients with cancer. Under these circumstances, self-report may underestimate respiratory distress. The Respiratory Distress Observation Scale is the first and only dyspnea assessment instrument designed to evaluate its presence and intensity in patients who are unable to communicate.

Key words: Breathlessness, Total dyspnea, Refractory dyspnea, Chronic dyspnea syndrome, Terminal dyspnea

RESUMEN

El concepto de “dificultad para respirar” enfatiza la naturaleza subjetiva multidimensional de la disnea con componentes físicos, psicológicos, sociales, espirituales y existencia­les. La “disnea total” aboga por un enfoque integral y centrado en el paciente más allá de la enfermedad. La noción de “disnea refractaria” debería ser evitada; implica cierto nihilismo terapéutico. Por tal motivo, se acuñó el concepto de “síndrome de disnea crónica” para reconocer las posibilidades de tratamiento y concientizar a los pacientes, los médicos, el equipo de salud y los investigadores. Las personas que viven con enfer­medades respiratorias avanzadas y disnea crónica grave (y sus allegados) tienen una mala calidad de vida. El modelo clínico-conceptual “respirando-pensando-funcionando” incluye las tres reacciones cognitivas y conductuales predominantes que, al provocar círculos viciosos, empeoran y mantienen el síntoma. Para la evaluación exhaustiva de la disnea se dispone de diversos instrumentos que consideran la experiencia sensorial-perceptiva, la angustia afectiva (distress) y el impacto o carga de los síntomas. La dificultad para respirar durante las últimas semanas o días de vida puede denominarse “disnea terminal”. Es un síntoma frecuente y uno de los más angustiantes en la última fase de la vida de pacientes con cáncer. En estas circunstancias el autorreporte puede subestimar la dificultad respiratoria. La Escala de Observación de Dificultad Respiratoria es el primer y único instrumento de evaluación de la disnea destinado a evaluar su presencia e intensidad en pacientes que no pueden comunicarse.

Palabras clave: Dificultad para respirar, Disnea total, Disnea refractaria, Síndrome de disnea crónica, Disnea terminal

Received: 01/08/2023

Accepted: 05/02/2024

MULTIDIMENSIONAL APPROACH TO DYSPNEA

The concept of “breathlessness” is widely used in the literature related to palliative care, instead of the biomedical term “dyspnea”, to emphasize the daily experience from the patient’s perspective.¹ The multidimensional subjective nature of dys­pnea goes beyond merely the physical condition and highlights the importance of the psychologi­cal, social, spiritual, and existential components. Similar to the concept of “total pain” described by Dame Cicely Saunders in the early 1960s, the concept of “total dyspnea” has been suggested, ad­vocating for a comprehensive and patient-centered approach beyond the disease itself.²

If dyspnea persists despite treatment of the underlying disease, it is sometimes referred to as “refractory dyspnea.” Since this term implies therapeutic nihilism, Johnson et al suggested call­ing it “chronic dyspnea syndrome” to acknowledge treatment possibilities and raise awareness among patients, physicians, healthcare teams, and re­searchers.² Chronic dyspnea syndrome is described as the sensation of breathlessness that persists despite receiving optimal treatment of the underly­ing physiopathology and causes disability.^3-5 Like total pain, total dyspnea encompasses multiple aspects and incorporates previously neglected constructs, such as the suffering related to the meaning patients assign to their symptoms. Total pain includes four domains: physical, psychologi­cal, interpersonal, and existential, and these are assessed from the patient’s perspective. Dyspnea is subjected to a similar analysis.⁶

For more than a decade, the respiratory sensa­tion (neural activation resulting from the activa­tion of peripheral receptors) and perception (con­scious and individual reaction to the sensation) have been clearly differentiated.⁷ Consequently, the sensation of dyspnea doesn’t need to be related to identifiable physiological factors. Patients’ ex­periences with dyspnea vary widely depending on factors such as ethnicity, experiences with other diseases, and emotional state. Additionally, various psychological and cultural factors can influence the reaction to a sensation. A stoic individual may not perceive (or deny) respiratory discomfort. The context in which the sensation occurs can also modify the perception of the sensory experience.^8-10

Anxiety, a particularly common psychological factor that correlates with dyspnea, can exacer­bate the symptom, leading to a progressive spiral of increased dyspnea and higher distress.^11,12 Epi­sodes of dyspnea can be predictable with known triggering factors, such as exertion, emotions, comorbidities, or the external environment, or they can appear to be unpredictable. Linde et al stated that many seemingly inexplicable episodes were known to have been driven by fear or panic when evaluated in depth.¹³

IMPACT OF DYSPNEA

Dyspnea often triggers panic, fear, anxiety, de­pression, hopelessness, a sense of loss of control, and a feeling of imminent death.^14,15 It also affects daily and social functions, leading to dependency and loss of roles. This symptom is one of the six parameters used in the Palliative Prognostic Score, which predicts the 30-day survival of patients in palliative care.¹⁶

A qualitative study illustrated the meaning of the dyspnea experience in patients with cancer, COPD (chronic obstructive pulmonary disease), heart failure, and amyotrophic lateral sclerosis (ALS):¹⁷

– For individuals with cancer, dyspnea serves not only as a sign of the presence of cancer but also as a reminder of mortality, even in the face of treatment optimism.

– In people with COPD, dyspnea is perceived as self-inflicted due to lifelong smoking.

– For those with heart failure, dyspnea is associ­ated with functional limitations and contributes to the negative effects of other symptoms.

– In individuals with ALS, dyspnea is related to mechanisms that are essential for living.

DYSPNEA AND QUALITY OF LIFE

People with advanced respiratory diseases and severe chronic dyspnea (and the people close to them) have a poor quality of life.^1,17 Chronic dyspnea is an incapacitating symptom, and acute episodes are terrifying to experience and observe. Many millions of people around the world live with advanced respiratory diseases, such as COPD and interstitial lung disease (ILD).¹⁸ These individuals aren’t receiving the palliative care they need to have the best possible quality of life.

These prevalent diseases, as well as other less common ones, can progress rapidly or have a more chronic course, and younger patients may be await­ing a lung transplant. However, in all cases, as the disease progresses, the patient becomes very symptomatic and is unlikely to improve despite maximum treatment of the underlying disease.

Although there is no comparable infrastructure for providing palliative care in non-oncological respiratory medicine, it is recognized that the deficit in symptom control and psychosocial sup­port leads to a poorer quality of life for patients not only with advanced respiratory diseases but also in the general population, and it is likely to have a negative effect on medical outcomes.¹⁹

ACUTE AND CHRONIC DYSPNEA AND PERSON-CENTERED CARE

Generally, more attention is given to the treat­ment of acute dyspnea than to chronic dyspnea. Therefore, it is the responsibility of every physician to provide the best person-centered care possible, ensuring the use of all available resources and knowledge.¹⁹

The term person-centered care, recognized as a hallmark of excellence in care, also encompasses the choice of specific treatments targeted at the disease, and provides a foundation for ensuring that patients receive individualized treatment, and that their symptoms and other concerns are identified. Healthcare professionals must play an active role in promoting quality of life as part of excellent medical care.

DYSPNEA IN TERMINAL RESPIRATORY DISEASE

The cardinal symptoms of advanced respiratory disease are persistent dyspnea, fatigue, and cough, sometimes referred to as the respiratory triad.^{20, 21} All these symptoms can be invisible at rest, so they need to be actively elicited to detect them. Scientific evidence for symptomatic treatments has improved in recent years; not using them in specialized respiratory care services should be considered inexcusable.

Other factors that greatly affect the outcomes and quality of life are outside the sphere of clinical influence, for example: financial anxiety, housing loss, lack of food, difficulty obtaining social as­sistance, concern about the continuity of health benefits, social isolation, caregiver burnout, and breakdowns in family relationships. Being outside the sphere of clinical influence does not mean they should be ignored.

THE EXISTENTIAL MEANING OF DYSPNEA

The spiritual repercussions of dyspnea can be strong. Just like pain, patients may attribute a variety of meanings to dyspnea, ranging from God’s punishment to a divine gift. Additionally, the patient’s religious or metaphysical beliefs can influence the extent of their suffering.^22-24 The secondary physiological and behavioral responses to dyspnea should be considered in the evalua­tion process. This concept has been subjected to experimental testing, supporting the hypothesis that the multiple dimensions or components can be measured as different entities. Some studies have demonstrated the existence of a separable “affective dimension” (i.e., distress and emotional impact).²⁵

SUBJECTIVE INDIVIDUAL EXPERIENCE

Dyspnea affects people in different ways and across different dimensions, which is well demonstrated by the Breathing, Thinking, Functioning clinical model.²¹ This model conceptualizes the three pre­dominant cognitive and behavioral reactions to dyspnea that, by creating vicious cycles, worsen and sustain the symptom (Figure 1).

Breathing domain: shortness of breath as­sociated with dysfunctional breathing patterns, increased respiratory rate, the need to use acces­sory muscles, and dynamic hyperinflation, leading to inefficient breathing and increased respiratory work.

Thinking domain: misconceptions about the nature of dyspnea, such as its cause, and previous experiences and memories that profoundly impact the current experience. This negative cognition and memories can cause anxiety, sadness, panic, and thoughts about death.

Functioning domain: individuals suffering from dyspnea often reduce their physical activity to avoid the sensation of breathlessness, leading to social isolation, increased dependence on others, and general deconditioning.

FAMILY IMPACT OF DYSPNEA

The dyspnea experienced by patients also af­fects informal caregivers (family and friends). However, their burden and anxieties are often overlooked and the existence of those feelings is normalized.²⁸

Caregivers of dyspnea patients perform many invisible caregiving tasks, such as hygiene, dress­ing, symptom control, and administering medica­tion and oxygen, in addition to all the household chores.²⁹ They also provide emotional support not only during the day but also through diffi­cult nights. They remain awake monitoring the patient’s breathing, and checking if they are still alive. Thus, it is not surprising for caregivers to report poor quality sleep, similar to people working shifts and mothers of young children.

Therefore, when treating patients with dyspnea, it is also necessary to focus on caregivers and their needs, providing them with education, support, and resources, just like for the patients. Caregivers should be encouraged to also take care of their own health, both physical and emotional.

EVALUATION AND IDENTIFICATION OF THE CAUSES OF DYSPNEA

The assessment of dyspnea must include the pa­tient’s subjective experience; therefore, the self-report of the symptom is essential. This should include the sensory component with its intensity and severity, the emotional burden reflected in the discomfort caused by dyspnea, and the impact on the patient’s daily life.

Currently, there is no universally accepted measure of health outcomes in clinical or research settings, which poses a clear barrier to routine clinical evaluation and follow-up of dyspnea.

The evaluation of a patient should also include a physical examination with vital signs and a cardio­pulmonary exam. Although additional diagnostic tests may be important to identify any treatable cause of dyspnea, it should be noted that more ob­jective evaluations, such as respiratory rate, blood gas analysis, or lung function tests do not mea­sure dyspnea and only moderately correlate with the patient’s subjective experience. For optimal management of dyspnea, treating the underlying disease and addressing reversible symptoms are the first step.

INSTRUMENTS FOR MEASURING DYSPNEA

For a comprehensive evaluation of its multidimen­sionality, an instrument must reflect each patient’s subjective sensory experience, provide an objective measurement of dyspnea, and facilitate the effec­tive communication with the healthcare team.³¹ There are three domains of dyspnea measurement proposed by the American Thoracic Society in 2012 and 2013.^11,12

1. Sensory-perceptual experience: this in­cludes the ratings of symptom intensity, frequency, duration, and sensory quality. The intensity of dys­pnea can be assessed using a Visual Analog Scale (VAS), the Borg Scale³², Likert-type ratings, or the Numeric Analog Scale (NAS). Dyspnea is also includ­ed in validated Spanish multidimensional assessment tools, such as the Memorial Symptom Assessment Scale and the Edmonton Symptom Assessment Scale (ESAS-r validated in Spanish).^33,34. For sensory qual­ity, Simon et al³⁵ reported 15 descriptors of dyspnea used by patients in eight groups (rapid, exhalation, shallow, effort, choking, hunger, tight, and heavy). The authors suggested possible associations of the descriptors with specific conditions causing dyspnea, but a subsequent study by Wilcock et al³⁶ could not demonstrate the robustness of these descriptors in helping with the diagnosis when applied to patients with cancer and cardiopulmonary diseases.³⁷

2. Affective distress: this can refer to immedi­ate distress or the distress that patients feel when they understand the meaning or consequences of their symptom. Discomfort can be rated as a single item, as in the case of dyspnea intensity. Scales with multiple items, such as the one for dyspnea in cancer, assess emotional responses, including anxiety.^38,39

Two validated measures, Dyspnoea 12 and the Multidimensional Dyspnea Profile (MDP), are suitable for use in both clinical and research settings and are brief enough for assessment and follow-up.^38-40

Dyspnoea 12 is a 12-item measure of dyspnea severity with 7 physical items and 5 affective items not related to physical activity. Response options are: none (0), mild (1), moderate (2), or severe (3). The time period refers to “these days.”^{40, 41}

The MDP is also a 12-item scale that uses scores (0-10). Seven items refer to overall intensity, unpleasantness, and other qualitative sensory descriptions of dyspnea (increased respiratory muscle work, chest tightness, air hunger, breath­ing a lot, requiring mental effort), and five rate the emotional responses to dyspnea (depression, anxiety, frustration, anger, and fear).^42,43

3. Impact or burden of symptoms: this includes the effect of dyspnea on behavior, func­tions, quality of life, or health status. The Medical Research Council (MRC) scale provides a unidi­mensional rating of disability,^44-46 while the Chronic Respiratory Disease Questionnaire (CRQ) is a multidimensional scale used for the assessment of functionality.^47-49

The MRC scale evaluates the consequences of dyspnea in relation to functional limitations. It is particularly useful if dyspnea is the only symptom experienced by the patient but is too insensitive to detect subtle changes after an intervention.⁸ Several quality of life scales have been validated for use in cancer or specifically for lung cancer and chronic lung diseases, such as the CRQ^47,48,50,51, EuroQol 5D, FACT-L⁵², QLQ-C15-PAL^53-55 and QLQ-LC13.^56,57 Table 2 summarizes the dyspnea assessment instruments and their main domains.

Currently, there are more than 50 scales for measuring dyspnea, covering several dimensions and different diseases.¹¹ However, there is no unified measurement tool for clinical use in the palliative care setting. It may be possible to com­bine the assessment of dyspnea intensity with its impact on the patient’s quality of life.⁵⁸ The NAS, the Modified Borg Scale, the CRQ dyspnea scale⁵⁹, the ALS Assessment Scale (based on the CRQ)⁶⁰ and the Cancer Dyspnea Scale seem to be the most suitable for the palliative care settings.⁶¹

Dyspnea can also be measured in terms of ex­ercise tolerance. Several instruments have been validated in advanced disease, namely, the Shuttle Walking Test⁶², the Reading Numbers Aloud Test⁶³, and the Upper Limbs Test.⁶⁴ Unfortunately, the fact that these tests are slow and expensive cur­rently limits their applicability in the clinical setting.⁵⁸

EVALUATION OF DYSPNEA CRISES

During crises, the patient is likely to experience an increase in intensity, distress, and fear.¹² Initially, dyspnea is often a component of several symptoms, including depression and anxiety. Self-report is the most valid and reliable method for assessing the patient’s experience, symptom progression, and response to treatment.

The simplest self-report is a dichotomous yes or no response to the question, “Are you short of breath?” However, yes or no responses are unlikely to help with palliative care, so the use of some rating of dyspnea intensity is expected. At least a standardized measure is recommended, such as the 0-10 Numerical Rating Scale, augmented by the evaluation of the patient’s subjective experience of distress and discomfort alongside the rating of dyspnea intensity.

TERMINAL DYSPNEA

Dyspnea suffered by patients during the last weeks or days of their life can be called “terminal dyspnea.”⁶⁵ Timely assessment and proactive management of dyspnea in these patients are of vital importance. This symptom has unique clini­cal characteristics: it tends to worsen rapidly over days or hours as death approaches, even despite symptom control measures. The family is also deeply affected, experiencing anxiety, uncertainty, helplessness, and inability. An assessment of the family-caregiver, the need for information, the desired level of participation in care, and home resources will support caregivers and integrate them into the healthcare team.

International guidelines have recently recog­nized that dyspnea is common and one of the most distressing symptoms in the final stages of life for cancer patients⁶⁶ and that patients have difficulty self-reporting the symptom. Since self-report is the gold standard for assessing dyspnea, there is a need to seek alternatives for this group of patients.

In clinical practice, healthcare teams conduct indirect assessments of symptom severity. How­ever, the accuracy of these subjective assessments may be poor. Studies conducted in advanced cancer populations and in intensive care units show that indirect assessments by physicians and nurses are significantly lower and poorly related to patient self-report. Given the fact that symptom severity assessments influence treatment decisions, a bet­ter method for assessing dyspnea in patients who cannot express themselves is necessary.

The Respiratory Distress Observation Scale (RDOS) is an ordinal 8-item scale designed to measure the presence and intensity of breathless­ness in adults. This scale was developed from a bio-behavioral framework by Campbell.^67,68 It is the first and only dyspnea assessment tool developed so far to evaluate its presence and intensity in pa­tients who are unable to communicate.^68-70 There are two modifications of the RDOS available for intensive care patients: the IC-RDOS (Intensive Care Respiratory Distress Observation Scale)^68,69,71 and the MV-RDOS (Mechanical Ventilation Respi­ratory Distress Observation Scale).⁷²

The RDOS demonstrates strong inter-rater reli­ability, convergent validity, and divergent validity, suggesting its reliability and validity as an assess­ment tool for palliative care patients.

Most importantly, it shows clinical utility by demonstrating good discriminative properties in detecting patients with moderate and severe dyspnea. A new RDOS cutoff point of ≥ 3 has been proposed for therapeutic intervention, with a sensitivity of 68% and a specificity of 77% for distinguishing between moderate to severe distress versus none (positive predictive value: 0.85 and negative predictive value: 0.61).^69,70 Table 3 shows the objective variables considered by the RDOS and the corresponding scores.

Seven patients (63.6 %) completed treatment, three patients (27 %) discontinued treatment, and one patient (9 %) passed away during the treatment. In terms of follow-up, one patient showed rifampicin resistance (patient with con­current lung involvement), and another patient (9 %) experienced reversible hepatotoxicity due to pyrazinamide.

The evaluation of the use of accessory muscles is based on the observation of the clavicle eleva­tion during inspiration. It does not refer to the palpation of accessory muscles such as the scalene, intercostals, sternocleidomastoid, or the contrac­tion of the abdominal muscles during expiration. Clavicle elevation somewhat reflects the activation of the upper thoracic and neck muscles and is an easy-to- identify sign.

The prevalence and severity of dyspnea increase at the end stages of life. Many of the patients in that situation have difficulty reporting their symptoms. Dyspnea is a symptom, only the per­son experiencing it can say that they are short of breath. Certain operational aspects of the use of Table 3 should be emphasized:

– The RDOS is used in adults and is not a sub­stitute for what the patient reports, as long as they can express it.

– The scale should not be used if the patient is paralyzed with a neuromuscular blocker and is not valid in cases of bulbar ALS or quadriplegia.

– Respiratory and heart rate can be measured during auscultation if necessary.

– Grunting can be audible even in intubated pa­tients through auscultation.⁶⁹

The RDOS is promising and has clinical util­ity as an observational dyspnea assessment tool. Further studies in less communicative patients are needed to determine clinical utility and the generalizability of the results.

CONCLUSIONS AND FUTURE APPROACH

It is not possible to address a person with dyspnea without considering its multidimensional subjec­tive nature, with its physical, psychological, social, spiritual, and existential components. The term “total dyspnea” encompasses these components. The term “refractory dyspnea” should be avoided and replaced by “chronic dyspnea syndrome” in order to recognize treatment possibilities and raise awareness among patients, physicians, healthcare teams, and researchers.

– People living with advanced respiratory diseases and severe chronic dyspnea (and the people close to them) have a poor quality of life.

– The Breathing-Thinking-Functioning clinical model includes the three predominant cognitive and behavioral reactions against dyspnea that worsen and maintain the symptom.

– There are various instruments available for the comprehensive assessment of dyspnea as a multidimensional symptom. These instruments propose considering the sensory-perceptual experience, affective distress, and the impact or burden of the symptoms.

– Dyspnea suffered by patients during the last weeks or days of their life can be called “termi­nal dyspnea.” It is a common symptom and one of the most distressing in the latest phase of life of patients with cancer.

– While the self-report of the sensation of breath­lessness is essential, some patients may not be able to express it, and it may be underestimated. The Respiratory Distress Observation Scale is the first and only dyspnea assessment instru­ment used to evaluate its presence and intensity in patients who are unable to communicate.

A better understanding of the brain processes underlying the perception of dyspnea will lead to new therapeutic approaches aimed at improving the quality of life for a very large group of patients.

REFERENCES

1. Booth S, Johnson MJ. Improving the quality of life of people with advanced respiratory disease and severe breathlessness. Breathe (Sheff) 2019;15:198-215. https://doi.org/10.1183/20734735.0200-2019

2. Johnson MJ, Currow DC, Booth S. Prevalence and assess­ment of breathlessness in the clinical setting. Expert Rev Respir Med 2014;8:151-61. https://doi.org/10.1586/17476348.2014.879530

3. Carel H, Macnaughton J, Dodd J. Invisible suffer­ing: breathlessness in and beyond the clinic. Lancet Respir Med 2015;3:278-9. https://doi.org/10.1016/S2213-2600(15)00115-0

4. Marjolein G, Higginson IJ. Access to Services for Pa­tients with Chronic Obstructive Pulmonary Disease: The Invisibility of Breathlessness. J Pain Symptom Man­age 2008;36:451-60. https://doi.org/10.1016/j.jpainsym­man.2007.11.008.

5. Morélot-Panzini C, Adler D, Aguilaniu B, et al. Dys­pnoea working group of the Société de Pneumologie de Langue Française. Breathlessness despite optimal pathophysiological treatment: on the relevance of be­ing chronic. Eur Respir J 2017;50:1701159. https://doi.org/10.1183/13993003.01159-2017.

6. Langford RM. Pain: nonmalignant disease for current opinion in supportive and palliative care. Curr Opin Sup­port Palliat Care 2008;2:114-5. https://doi.org/10.1097/SPC.0b013e32830139d5.

7. Guz A. Brain, breathing and breathlessness. Respir Physiol 1997;109:197-04. https://doi.org/10.1016/S0034- 5687(97)00050-9

8. Mahler DA, O’Donnell DE. Dyspnea: Mechanisms, Mea­surement, and Management, Third Edition. CRC Press, 2014. https://doi.org/10.1201/b16363

9. Mahler, Donald (1991). Dyspnea. Medicine & Sci­ence in Sports & Exercise 1991;23:1322. https://doi.org/10.1249/00005768-199111000-00027.

10. Mahler DA. Understanding mechanisms and document­ing plausibility of palliative interventions for dyspnea. Curr Opin Support Palliat Care 2011;5:71-6. https://doi.org/10.1097/SPC.0b013e328345bc84

11. Parshall MB, Schwartzstein RM, Adams L, et al. An offi­cial American Thoracic Society statement: update on the mechanisms, assessment, and management of dyspnea. Am J Respir Crit Care Med 2012;185:435-52. https://doi.org/10.1164/rccm.201111-2042ST

12. Mularski RA, Reinke LF, Carrieri-Kohlman V, et al. An Of­ficial American Thoracic Society Workshop Report: Assess­ment and Palliative Management of Dyspnea Crisis. Ann Am Thorac Soc 2013;10:S98-S106. https://doi.org/10.1513/AnnalsATS.201306-169ST

13. Linde P, Hanke G, Voltz R, Simon ST. Unpredictable episodic breathlessness in patients with advanced chronic obstructive pulmonary disease and lung cancer: a qualita­tive study. Support Care Cancer 2018;26:1097-104. https://doi.org/10.1007/s00520-017-3928-9.

14. Gysels M, Bausewein C, Higginson IJ. Experiences of breathlessness: A systematic review of the qualitative literature. Palliat Support Care 2007;5:281-302. https://doi.org/10.1017/S1478951507000454

15. Simon ST, Higginson IJ, Benalia H, et al. Episodes of breath­lessness: Types and patterns – a qualitative study exploring experiences of patients with advanced diseases. Palliat Med 2013;27:524-32. https://doi.org/10.1177/0269216313480255

16. Pirovano M, Maltoni M, Nanni O, et al. A New Palliative Prognostic Score. J Pain Symptom Manage 1999;17:231-9. https://doi.org/10.1016/S0885-3924(98)00145-6

17. Gysels M, Higginson IJ. Access to services for patients with chronic obstructive pulmonary disease: the invisibility of breathlessness. J Pain Symptom Manage 2008;36:451-60. https://doi.org/10.1016/j.jpainsymman.2007.11.008

18. World Health Organization. Chronic respiratory diseases. https://www.who.int/health-topics/chronic-respiratory-diseases#tab=tab_1. 2023.

19. Currow DC, Dal Grande E, Ferreira D, et al. Chronic breathlessness associated with poorer physical and mental health-related quality of life (SF-12) across all adult age groups. Thorax 2017;72:1151-3. https://doi.org/10.1136/thoraxjnl-2016-209908

20. Yorke J, Lloyd-Williams M, Smith J, et al. Management of the respiratory distress symptom cluster in lung cancer: a randomized controlled feasibility trial. Support Care Cancer 2015;23:3373-84. https://doi.org/10.1007/s00520-015-2810-x

21. Yorke J, Johnson MJ, Punnett G, et al. Respiratory distress symptom intervention for non-pharmacological manage­ment of the lung cancer breathlessness–cough–fatigue symptom cluster: randomised controlled trial. BMJ Sup­port Palliat Care 2022;spcare–2022. https://doi.org/10.1136/spcare-2022-003924

22. Langford RM. Pain: nonmalignant disease for current opinion in supportive and palliative care. Curr Opin Sup­port Palliat Care 2008;2:114-5. https://doi.org/10.1097/SPC.0b013e32830139d5120

23. Booth S. Science Supporting the Art of Medicine: Im­proving the Management of Breathlessness. Palliat Med 2013;27:483-5. https://doi.org/10.1177/0269216313488490.

24. Hutchinson, A. Patient and carer experience of breath­lessness. In C. Bausewein, D. C. Currow, & M. J. John­son (Eds.), Palliative Care in Respiratory Disease 2016 (102-110). European Respiratory Society. https://doi.org/10.1183/2312508X.10011615

25. Lansing RW, Gracely RH, Banzett RB. The multiple dimensions of dyspnea: review and hypotheses. Respir Physiol Neurobiol 2009;167:53-60. https://doi.org/10.1016/j.resp.2008.07.012

26. Spathis A, Booth S, Moffat C, et al. The Breathing, Think­ing, Functioning clinical model: a proposal to facilitate evidence-based breathlessness management in chronic respiratory disease. NPJ Prim Care Respir Med 2017;27:27. https://doi.org/10.1038/s41533-017-0024-z.

27. Spathis A, Burkin J, Moffat C, et al. Cutting through complexity: the Breathing, Thinking, Functioning clini­cal model is an educational tool that facilitates chronic breathlessness management. NPJ Prim Care Respir Med 2021;31:25. https://doi.org/10.1038/s41533-021-00237-9.

28. Veloso VI, Tripodoro VA. Caregivers burden in pallia­tive care patients: a problem to tackle. Curr Opin Sup­port Palliat Care 2016;10:330-5. https://doi.org/10.1097/SPC.0000000000000239.

29. Farquhar M. Supporting informal carers. Palliative Care in Respiratory Disease. Eur Respir Monogr 2016;73:51-69. https://doi.org/10.1183/2312508X.10011315

30. Bruera E, Higginson EJ, von Gunten CF, Morita T. Text­book of Palliative Medicine and Supportive Care 2021, CRC Press, https://doi.org/10.1201/9780429275524.

31. Chan K-S, Tse DMW, Sham MMK. Dyspnoea and other respiratory symptoms in palliative care. Oxford Textbook of Palliative Medicine 2015;421-34. https://doi.org/10.1093/med/9780199656097.003.0082

32. Borg GAV. Psychophysical bases of perceived exer­tion. Med Sci Sports Exer 1982;14:377-81. https://doi.org/10.1249/00005768-198205000-00012

33. Carvajal A, Hribernik N, Duarte E, et al. The Spanish Version of the Edmonton Symptom Assessment System- Revised (ESAS-r): First Psychometric Analysis Involving Patients with Advanced Cancer. J Pain Symptom Man­age 2013;45:129-36. https://doi.org/10.1016/j.jpainsym­man.2012.01.014

34. Llamas-Ramos I, Llamas-Ramos R, Buz J, et al. Construct Validity of the Spanish Versions of the Memorial Symp­tom Assessment Scale Short Form and Condensed Form: Rasch Analysis of Responses in Oncology Outpatients. J Pain Symptom Manage 2018;55:1480-91. https://doi.org/10.1016/j.jpainsymman.2018.02.017

35. Simon PM, Schwartzstein RM, Weiss JW, Fencl V, Teght­soonian M, Weinberger SE. Distinguishable Types of Dyspnea in Patients with Shortness of Breath. Am Rev Respir Dis 1990;142:1009-14. https://doi.org/10.1164/ajrccm/142.5.1009

36. Wilcock A, Crosby V, Hughes A, Fielding K, Corcoran R, Tattersfield AE. Descriptors of breathlessness in patients with cancer and other cardiorespiratory diseases. J Pain Symptom Manage. 2002;23:182-9. https://doi.org/10.1016/S0885-3924(01)00417-1

37. Chowienczyk S, Javadzadeh S, Booth S, Farquhar M. As­sociation of Descriptors of Breathlessness With Diagnosis and Self-Reported Severity of Breathlessness in Patients With Advanced Chronic Obstructive Pulmonary Disease or Cancer. J Pain Symptom Manage 2016;52:259-64. https://doi.org/10.1016/j.jpainsymman.2016.01.014

38. Tanaka K, Akechi T, Okuyama T, Nishiwaki Y, Uchitomi Y. Development and validation of the Cancer Dyspnoea Scale: a multidimensional, brief, self-rating scale. Br J Cancer 2000;82:800-5. https://doi.org/10.1054/bjoc.1999.1002

39. Kimpara K, Shinichi A, Maki T, Yuichi T. Working Memory Impacts Endurance for Dyspnea. Physiotherapists, Eur Respir J 2020;56:2455. https://doi.org/10.1183/13993003.congress-2020.2455.

40. Williams MT, John D, Frith P. Comparison of the Dys­pnoea-12 and Multidimensional Dyspnoea Profile in people with COPD. Eur Respir J 2017;49:1600773. https://doi.org/10.1183/13993003.00773-2016.

41. Koskela J, Kupiainen H, Kilpeläinen M, et al. Longitudinal HRQoL shows divergent trends and identifies constant de­cliners in asthma and COPD. Respir Med 2014;108:463-71. https://doi.org/10.1016/j.rmed.2013.12.001

42. Meek PM, Banzett R, Parsall MB, et al. Reliability and validity of the multidimensional dyspnea profile. Chest 2012;141:1546-53. https://doi.org/10.1378/chest.11-1087.

43. Belo LF, Rodrigues A, Vicentin AP, et al. A breath of fresh air: Validity and reliability of a Portuguese version of the Multidimensional Dyspnea Profile for patients with COPD. PLoS One 2019;14:e0215544. https://doi.org/10.1371/jour­nal.pone.0215544.

44. Mahler DA, Wells CK. Evaluation of Clinical Methods for Rating Dyspnea. Chest 1988;93:580-6. https://doi.org/10.1378/chest.93.3.580

45. Guidance Respiratory questionnaire and instructions to interviewers (1966) https://www.ukri.org/publications/respiratory-questionnaire-and-instructions-to-interview­ers-1966/.

46. Güell R, Casan P, Sangenís M, et al. Traducción española y validación de un cuestionario de calidad de vida en paci­entes con enfermedad pulmonar obstructiva crónica. Arch Bronconeumol 1995;31:202-10. https://doi.org/10.1016/S0300-2896(15)30925-X

47. Guyatt GH, Berman LB, Townsend M. Long-term outcome after respiratory rehabilitation. CMAJ 1987;137:1089–95.

48. Guyatt GH, Berman LB, Townsend M, Pugsley SO, Cham­bers LW. A measure of quality of life for clinical trials in chronic lung disease. Thorax 1987;42:773-8. https://doi.org/10.1136/thx.42.10.773.

49. Guyatt GH, Townsend M, Berman LB, et al. A comparison of Likert and visual analogue scales for measuring change in function. J Chronic Dis 1987;40:1129-33. https://doi.org/10.1016/0021-9681(87)90080-4

50. Valero-Moreno S, Castillo-Corullón S, Prado-Gascó VJ, Pérez-Marín M, Montoya-Castilla I. Chronic Respiratory Disease Questionnaire (CRQ-SAS): Analysis of psycho­metric properties. Arch Argent Pediatr 2019;117:149-56. https://doi.org/10.5546/aap.2019.eng.149.

51. Guyatt GH, Townsend M, Berman LB, Pugsley SO. Qual­ity of life in patients with chronic airflow limitation. Br J Dis Chest. 1987;81:45-54. https://doi.org/10.1016/0007-0971(87)90107-0.

52. Cella DF, Bonomi AE, Lloyd SR, et al. Reliability and validity of the functional assessment of cancer therapy-lung (FACT-L) quality of life instrument. Lung Cancer 1995;12:199-220. https://doi.org/10.1016/0169-5002(95)00450-F121

53. Groenvold M, Petersen MA, Aaronson NK, et al. The devel­opment of the EORTC QLQ-C15-PAL: A shortened ques­tionnaire for cancer patients in palliative care. Eur J Cancer 2006;42:55-64. https://doi.org/10.1016/j.ejca.2005.06.022

54. Groenvold M, Petersen MA, Aaronson NK, et al. EORTC QLQ-C15-PAL: the new standard in the as­sessment of health-related quality of life in ad­vanced cancer? Palliat Med 2006;20:59-61. https://doi.org/10.1191/0269216306pm1090ed

55. Pilz MJ, Aaronson NK, Arraras JI, et al. Evaluating the Thresholds for Clinical Importance of the EORTC QLQ-C15-PAL in Patients Receiving Palliative Treatment. J Palliat Med 2021;24:397-404. https://doi.org/10.1089/jpm.2020.0159.

56. Bergman B, Aaronson NK, Ahmedzai S, et al. The EORTC QLQ-LC13: a modular supplement to the EORTC core qual­ity of life questionnaire (QLQ-C30) for use in lung cancer clinical trials. Eur J Cancer 1994;30:635-42. https://doi.org/10.1016/0959-8049(94)90535-5

57. Nicklasson M, Bergman B. Validity, reliability and clinical relevance of EORTC QLQ-C30 and LC13 in patients with chest malignancies in a palliative setting. Qual Life Res 2007;16:1019-28. https://doi.org/10.1007/s11136-007-9210-8.

58. Bausewein C, Farquhar M, Booth S, et al. Measurement of breathlessness in advanced disease: A systematic review. Respir Med 2007;101:399-410.

59. Lovell N, Etkind SN, Bajwah S, et al. To What Extent Do the NRS and CRQ Capture Change in Patients’ Experience of Breathlessness in Advanced Disease? Findings From a Mixed-Methods Double-Blind Randomized Feasibility Trial. J Pain Symptom Manage 2019;58:369-81.e7. https://doi.org/10.1016/j.jpainsymman.2019.06.004

60. Bourke SC, McColl E, Shaw PJ, Gibson GJ. Validation of quality of life instruments in ALS. Amyotroph Lateral Scler Other Motor Neuron Disord 2004;5:55-60. https://doi.org/10.1080/14660820310016066.

61. Dorman S, Byrne A, Edwards A. Which measurement scales should we use to measure breathlessness in palliative care? A systematic review. Palliat Med 2007;21:177-91. https:// doi.org/10.1177/0269216307076398.

62. Booth S, Adams L. The shuttle walking test: a reproduc­ible method for evaluating the impact of shortness of breath on functional capacity in patients with advanced cancer. Thorax 2001;56:146-50. https://doi.org/10.1136/thorax.56.2.146.

63. Wilcock A, Crosby V, Clarke D, et al. Reading numbers aloud: a measure of the limiting effect of breathlessness in patients with cancer. Thorax 1999;54:1099-103. https://doi.org/10.1136/thx.54.12.1099

64. Wilcock A, Walker G, Manderson C, et al. Use of Upper Limb Exercise to Assess Breathlessness in Patients with Cancer: Tolerability, Repeatability, and Sensitivity. J Pain Symptom Manage 2005;29:559-64. https://doi.org/10.1016/j.jpainsymman.2004.09.003

65. Mori M, Yamaguchi T, Matsuda Y, et al. Unanswered questions and future direction in the management of terminal breathlessness in patients with cancer. ESMO Open 2020;5 Suppl 1: e000603. https://doi.org/10.1136/esmoopen-2019-000603.

66. Koller M, Warncke S, Hjermstad MJ, et al. European Orga­nization for Research and Treatment of Cancer (EORTC) Quality of Life Group; EORTC Lung Cancer Group. Use of the lung cancer-specific Quality of Life Questionnaire EORTC QLQ-LC13 in clinical trials: A systematic review of the literature 20 years after its development. Cancer 2015;15;121:4300-23. https://doi.org/10.1002/cncr.29682.

67. Campbell ML. Psychometric testing of a respiratory distress observation scale. J Palliat Med 2008;11:44-50. https://doi.org/10.1089/jpm.2007.0090.

68. Campbell ML, Templin T, Walch J. A Respiratory Distress Observation Scale for patients unable to self-report dys­pnea. J Palliat Med 2010;13:285-90. https://doi.org/10.1089/jpm.2009.0229.

69. Zhuang Q, Yang GM, Neo SH-S, et al. Validity, Reliability, and Diagnostic Accuracy of the Respiratory Distress Obser­vation Scale for Assessment of Dyspnea in Adult Palliative Care Patients. J Pain Symptom Manage 2019;57:304-10. https://doi.org/10.1016/j.jpainsymman.2018.10.506

70. Chesteen K, Kothare N, Huth H, Misra S. Implementing a Respiratory Distress Scale for Unconscious Patients in a Palliative Care Unit. J Pain Symptom Manage 2022;63:871. https://doi.org//10.1016/j.jpainsymman.2022.02.063.

71. Decavèle M, Rivals I, Persichini R, et al. Prognostic Value of the Intensive Care Respiratory Distress Observation Scale on ICU Admission. Respir Care 2022;67:823-32. https://doi. org/10.4187/respcare.09601

72. Decavèle M, Rozenberg E, Niérat M-C, et al. Respiratory distress observation scales to predict weaning outcome. Crit Care 2022;26:162. https://doi.org/10.1186/s13054-022- 04028-712