Chronic breathlessness in fibrotic interstitial lung diseases—patient centered assessment and management in outpatient settings

Introduction

Background

Fibrotic interstitial lung diseases (F-ILDs) are a group of heterogenous pulmonary conditions characterized by inflammation and scarring (1). Chronic breathlessness (CB) or dyspnea, a cardinal symptom of F-ILD, is defined as dyspnea that persists despite optimal treatment of underlying conditions (2). The estimated prevalence of CB in F-ILD ranges from 58% to 98% (3). It is the presenting feature in 90% of these patients, often preceding diagnosis by 7 months to 4 years (3,4). In idiopathic pulmonary fibrosis (IPF), a common idiopathic F-ILD, 1 in 10 patients experience severe CB of modified medical research council (mMRC) grade 4, and those with mMRC grade ≥3 have a median survival of 0.5 years (5,6). It is a potent driver of poor health-related quality of life (HRQOL), with increased morbidity and mortality, and escalating hospitalization rates with associated costs as the disease progresses. Over 70% of IPF patients were also noted to have demoralization syndrome in a recent study (defined as loss of meaning in life, hopelessness and helplessness and feelings of failure) (7). This likely stems from underlying fears, anxiety, depression, loss of function and independence from untreated CB (Figure 1). Thus, CB leads to serious health-related suffering and distressing end-of-life (EoL) experiences for these patients (8-12). Despite its high prevalence and severe consequences, targeted CB assessment and interventions are often not implemented (13). There are several evidence-based interventions for CB in various non-malignant diseases that improve patient outcomes but they are not routinely implemented in care (14,15). The under recognition and undertreatment of CB represent a lost opportunity to minimize morbidity, mortality, and most importantly, alleviate the suffering of patients and their families (16).

Figure 1 Impact of untreated chronic dyspnea in ILD. ILD, interstitial lung disease.

Recognizing the importance of breathlessness management, recent European and American guidelines recommend early integration of palliative care (PC) into usual care for all chronic respiratory diseases including F-ILD (17-19). Unfortunately, physicians often lack knowledge and dedicated training in symptom management, expressing difficulty in decision-making regarding appropriate timing for initiating conversations, treatments, and referrals to PC specialists (20,21). Thus, making the implementation of guidelines-based recommendations very challenging. A recent survey of pulmonologists identified barriers to successful management of CB in F-ILD and the need for improved dissemination of breathlessness management guidelines (22). While ILD specialists and teams are more aware of CB needs and willing to refer patients to PC specialist, integration of CB management in routine care is lacking even within ILD centers (20,23,24).

Objective

This narrative review aims to summarize the current literature on CB assessment and management in F-ILD. It highlights the necessity for a systematic, holistic approach to assessment and the sequential implementation of CB therapies for enhanced patient care. A patient centered stepwise CB management approach for F-ILD is proposed based on needs, gaps in care and available evidence.

CB assessment in F-ILD: role of dyspnea domains and the use of, validated measurement tools combined with a narrative approach

Breathlessness is a challenging symptom to assess likely due to multiple factors including complex neurophysiology that is influenced by patient’s psychological state, and other input from the corticolimbic systems. The CB perception itself is made worse by the patients’ reaction to CB. Therefore, CB as a symptom has a multidimensional construct of distinct domains: sensory-perceptual, affective, and impact or burden that capture the physical, emotional and psychological aspects of the patient experience. A subsequent study has identified control and context as additional domains of importance to patients (25) (Figure 2). A recent systematic review recommended the use of 4 validated multidimensional tools for CB assessment in F-ILD, Dypnsea-12, UCSD-shortness of breath questionnaire, EXAcerbations of Chronic Obstructive Pulmonary Disease Tool (EXACT)-Respiratory Symptoms Idiopathic Pulmonary Fibrosis Breathlessness subscale (ERS-IPF-B) and King’s Brief Interstitial Lung Disease Health Status Questionnaire breathlessness and activities subscale (KBILD-B) (26). These tools variably measure some but not all dimensions of this complex experience (Table 1). In real-world practice, it has not been feasible to use these tools in busy clinics due to the large numbers of questions and/or the complex response systems used in these tools. Therefore, unidimensional tools are more prevalent in clinical practice (27). The MRC or mMRC are the most frequently used tools that provide an estimate of breathlessness-induced limitation rather than its severity or the precise impact of breathlessness in daily life (22,27-29). These validated scales are brief and easy to use in clinical practice, but may not be sufficient for assessing and managing CB (28,30). Numeric rating scale (NRS) like the Edmonton symptom assessment scale, commonly used by palliative experts can assess dyspnea severity but not the other domains. Additionally, ILD patients most often experience exertional breathlessness and may look comfortable at rest, therefore a systematic enquiry about exertional dyspnea in the context of activities of daily living (ADL) is essential to identify needs and target interventions (31-33). MRC/mMRC or NRS do not provide such type of detailed dyspnea severity assessment with various daily activities or align with what patients want (Figure 3).

Figure 2 Multidimensional construct of chronic breathlessness.

Figure 3 What do fibrotic interstitial lung disease patients want from breathlessness management?

Therefore, a patient-centered assessment of CB in F-ILD must not only identify breathlessness, but also assess its varying severity with ADL, that is of practical concern to most ILD patients (34). It should also assess for CB associated crises arising from patient’s diminishing sense of control and increasing hopelessness as the disease progresses (35). Crisis breathlessness is a well-defined entity, described in many advanced diseases that leads to significant physical and psychosocial distress, acute care use and is therefore, important to identify during CB assessment (36). This has been reported by F-ILD patients (37). Assessment of coping and in particular maladaptive patterns, thoughts, beliefs must be identified and corrected as they can negate or subvert treatment benefits. Caregiver needs for education and support must also be identified during clinic assessment. It is unlikely for a single tool to assess all the above, therefore a narrative approach is also required (26). Thus a patient-centered CB assessment requires an engaged clinician who will “listen to” the patients, their families to meaningfully interpret the data provided by the instruments and go beyond the numbers to include the person reporting them (Figure 4) (32,38).

Figure 4 Patient-centered chronic breathlessness assessment.

CB management in F-ILD: review of evidence-based interventions

There are many potential interventions for breathlessness in ILD (21). After optimization of the underlying disease therapy, a hierarchical or stepwise approach to CB management is suggested: (I) introduction of nonpharmacologic interventions (NPI) followed by, (II) oxygen and (III) introduction of pharmacological treatment (39). Optimizing underlying F-ILD management is beyond the scope of this review and will not be covered here. While recent advances in genetic and molecular research, and introduction of antifibrotics therapies that slow disease progression hold great potential to improve F-ILD care, none of these therapies adequately address patients’ symptoms or improve HRQOL (40). Therefore, targeted CB management is needed. Major CB therapies are summarized in Tables 2,3 and ILD relevant interventions are reviewed below.

NPI

NPI are a diverse group of single or multicomponent interventions with several different mechanisms of action. NPI are considered the most effective interventions currently available to palliate CB in ambulatory patients with chronic respiratory disease and cancer (14,70-72). They are the first step in CB management, unfortunately, real-world practice patterns in F-ILD suggest they are rarely used or optimized in practice (Table 4) (39).

Pulmonary rehabilitation (PR), the most well studied multicomponent NPI in F-ILD, is a behavioral modification intervention consisting of supervised group exercises and education delivered by a multidisciplinary team over several weeks (42). Participation in pulmonary rehabilitation improved functional capacity, dyspnea and HRQOL with low to moderate certainty of evidence in F-ILD patients (41). Unfortunately, its uptake remains low even within ILD centers due to many factors such as increased symptom burden, frailty, dependence on high-flow oxygen that makes transportation challenging along with other access issues (75). Consequently, feasibility of a home-based PR interventions is being explored. A pilot study of 21 F-ILD patients showed some improvements in CB and HRQOL, but was underpowered for efficacy analysis. Many participants reported positive program impact on their ability to adapt and cope with their disease, an unmet CB need in F-ILD (76). Bassi et al. examined a multidisciplinary clinic-based model that focused on NPI measures for CB and used a PR-based approach in the clinic setting and demonstrated a positive impact on CB in F-ILD (77).

The use of hand-held fans (HHFs) reduces breathlessness intensity and improves physical activity in patients with many respiratory (78). Different airflow speeds from HHF have been found to modify breathlessness during exercise recovery, with higher airflow rates leading to faster recovery (79). In a recent feasibility trial, the use of HHF was acceptable to many F-ILD patients; a randomized controlled trial (RCT) is awaited (43). Self-management education and action plans improve outcomes in chronic obstructive pulmonary disease (COPD) and early data suggests benefit in F-ILD (45,80). Other studies are awaited (48,49) (Table 2). Symptom action plans include patient instructions on how to relax, change posture, use oxygen and as needed opioids for dyspnea crisis. Health coaching embedded with PR was also noted to be beneficial in a small pilot study (76). Other NPIs including breathing techniques have either not shown benefit in F-ILD or only suggest feasibility at this stage and are summarized in Table 2 (44,50). Many of these strategies were found to be effective in other respiratory conditions and are likely effective in ILD, for example, energy conservation strategies, ADL and respiratory retraining, relaxation etc. (46). In practice, most NPIs need to be personalized to an individual’s functional status, preference and motivation for learning a new skill or technique and their cognition. Some NPI may be more suitable at certain points of the disease trajectory. As the disease advances, many NPIs that require motivation and learning cannot be used as patients become physically or mentally fatigued suggesting that proper timing of therapies is important (71). Many other beneficial NPIs such as activity and behavior modifications, use of aids and devices, breathing techniques, postures, relaxation are in use in some ILD care models, breathlessness services and are reportedly also adopted by F-ILD patients as part of self-management education (45,71,74,81). Unfortunately, evidence of efficacy is limited as they are not well studied outside occupational and physiotherapy literature (14). In addition, there are several barriers to their implementation. NPI require trained and dedicated allied staff and/or clinicians’ support for early, appropriate prescriptions and ongoing monitoring. Clinicians often lack NPI knowledge and experience due to minimal symptom management curricula in training. Another challenge to their adoption is need for a health coaching approach for patient buy-in and adherence and the need for multidisciplinary support in outpatient settings. Clear guidance and training may help clinicians identify the right NPI, right patient, right time as well the right combination of strategies to use. Patient and clinician engagement is key to successful NPI use as demonstrated by practice audits of ILD clinics where symptoms prioritization by clinicians and their engagement in integrated symptom management resulted in NPI use in up to 98% IPF outpatients (activity or behavior modification i.e., pacing or energy conservation strategies) (74). Other strategies such as non-invasive ventilation use in exercise, with acute and chronic respiratory failure and EoL use appear to provide some benefit and are reviewed in Table 2 (51-53).

Oxygen

Exertional hypoxemia (EH), a hallmark of early ILD, frequently causes dyspnea, and activity intolerance (82). It is an important marker of disease progression and an independent predictor of mortality. Progressive F-ILD leads to worsening EH and finally resting hypoxemia (RH) (83,84). Oxygen therapy is frequently used to improve symptoms and HRQOL. The mechanisms by which supplemental oxygen improves dyspnea in hypoxemic patients are not well understood, but could include reduction in respiratory drive, changes in breathing pattern, and/or stimulation of upper airway receptors by gas flow as well as chemoreceptor activation and the resolution of hypoxemia that occurs in a dose responsive fashion (85,86). Ambulatory oxygen use has been shown to alleviate dyspnea, cough and impaired exercise performance in F-ILD in a short-term trial (54,87) and only exercise capacity in a different systematic review (55). A recent systematic review identified that oxygen helped patients increase activity, independence, confidence and sense of control but some had unmet expectations and identified it with deterioration (88). Outcomes on long-term oxygen therapy in ILD are awaited but improved survival in COPD have been extrapolated, leading to strong recommendations of using long-term oxygen therapy in ILD patients with RH and conditional recommendation in those with isolated severe EH (56,89).

Unfortunately, there is limited guidance on when to initiate oxygen for EH, how to prescribe (various flow rates for different activities), monitor and titrate oxygen, and provide education to patients and caregivers. Most ILD experts recommend oxygen for symptomatic patients when nadir exertional oxygen saturation <85–89% (90). Resting and exertional hypoxemia risk prediction tools are being developed and validated. They utilize easily available clinical data such as age, diagnosis, body mass index, lung function parameters for risk estimation (91,92). Their use may help identify patients at risk and lead to early oxygen start. Currently, EH is identified through a formal 6-minute walk test that is labor-intensive and not easily accessible in the community. In addition, clinicians must determine individual oxygen flow rates for rest, sleep and various activities as this can vary significantly in F-ILD. There are many different types of oxygen delivery systems and their adequacy to meet patient needs changes over time requiring close follow up. Patients also need advice on when to use pulse versus continuous flows. Many patients prefer to use portable concentrators that often cannot meet their oxygen needs. Many mistakenly use pulse and continuous flow interchangeably, not knowing that 6 pulse and 6 liters per minute (LPM) are not the same. The type of delivery system a patient receives will have a significant impact on activity, symptoms and therefore, HRQOL (93). Many physicians and respiratory therapists are not aware of these nuances and therefore may not be able to provide appropriate advice (94). Currently, decisions regarding delivery systems, monitoring frequency and titrations, are largely left to individual physicians and oxygen providers; and in the absence of guidance such practices are not standardized (95). Thus, proper oxygen prescription and monitoring requires clinicians to have basic knowledge of home and ambulatory oxygen delivery systems, in addition to, actively engaging with the patients and oxygen providers to ensure needs are met. Thus, oxygen therapy-related basic knowledge is important for PC experts who will be increasingly called upon to provide CB management advice. Education on outpatient oxygen use is not common in pulmonary or PC education and needs to be incorporated into training (96,97). In addition, there are limited reports on how to manage high flow oxygen use in the community (i.e., >15 LPM), a common occurrence in progressive F-ILD. Increasing provider competency in outpatient oxygen therapy will facilitate the patient centered goal of living and dying well at home while on high flow oxygen (98-100). Inpatient high flow oxygen has been shown to be effective in ILD in the short term (57,58).

It is important to recall that the uptake and adherence to oxygen therapy is highly variable and complex. It is determined by patient, provider, therapy and system characteristics. Patient perceived burden of therapy include cumbersome equipment, stigmatization, social isolation and lack of self-management education and community oxygen supports. Access to a consistent person with procedural knowledge about oxygen is also an important facilitator (88). Thus, physician acknowledgement, support and encouragement are vital to ensure proper oxygen use and perceived patient benefit. Technological innovation is also required to make oxygen therapy less cumbersome, with lightweight, portable equipment to meet high flow needs.

Opioids

Opioids are the most studied pharmacologic agents for relieving CB. To date, only two small double-blinded, placebo-controlled, RCTs have examined the impact of opioids in F-ILD. The 2 RCTs examined immediate-release 5 mg every 6 hours and 20 mg of sustained-release oral morphine respectively. The former was ineffective for breathlessness reduction compared to placebo after 1 week but the authors opined that the direction of signal favored morphine (63). The second study, a crossover RCT did not reach the pre-planned sample size. Therefore, the findings were considered exploratory but the direction of signal also favored (64) (Table 3). Unfortunately, neither RCT described optimization of NPI or oxygen in any detail prior to morphine use. The stepwise CB approach recommends pharmacotherapy only after optimization of NPI and oxygen use. Thus, not ensuring the “right time” for morphine start may have impacted the results in both cases (101). Post-hoc analysis of other RCT data indicates that opioids may indeed be effective in a select group of patients with more functional impairment and more advanced disease (102). Unfortunately, the chosen inclusion criteria in the above referenced RCTs (MRC ≥3 and mMRC ≥2 respectively at baseline) may not have selected for the group most likely to respond. Real-world practice also suggests that opioids are often prescribed to patients with significant functional impairment with >90% opioid initiations occurring at EoL in one study (103). This group likely has poor HRQOL with significant CB-related impairment where minimal improvement in function may be perceived as net benefit by the patient (102,104). In a single center study with integrated symptom management within an ILD clinic, opioids were started at median 4 months prior to deaths after optimization of NPI and oxygen (84). Despite the above listed methodologic concerns, the RCT results are encouraging and results from other larger well-designed studies in F-ILD are awaited (105).

Given limited evidence experts recommend low-dose opioids only for individuals who remain breathlessness despite optimization of NPI and oxygen and who are likely at an advanced state of disease and in distress (106,107). Both the American Thoracic Society and American College of Chest Physicians dyspnea guidelines as well as IPF clinical practice guidelines suggest systemic opioids as a therapeutic option for the symptomatic reduction of CB (38,86,89). Proposed mechanisms whereby opioids relieve breathlessness include: decreasing respiratory drive with an associated decrease in corollary discharge; altering central perception; altering activity of peripheral opioid receptors located in the lung and decreasing anxiety. Most common starting doses are 1–10 mg oral morphine with recommended follow up within 1 week to assess response and make dose adjustments (108-110). A systematic review in COPD suggests that sustained-release opioids do not improve dyspnea. Short-acting opioids appear to be safe, have the potential to lessen dyspnea, supporting its benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnea. These findings require further confirmation (111). The use of benzodiazepines and antidepressants for management of CB is not supported (Table 3). Others such as L-menthol are being examined in trials (69).

CB support services and care models

Specialized CB care models consist of multidisciplinary teams of allied staff, nurses and may include PC and/or respiratory physicians. They are dedicated to CB management. CB management involves identifying the most suitable interventions based on patient needs and personalizing them to the patient context, e.g., NPIs. Given all the barriers to symptom integration in routine care and in particular NPI implementation in real world clinics, such models are emerging as patient and family centered options. These models facilitate holistic CB assessment and undertake stepwise implementation of NPIs, oxygen and pharmacotherapies based on patients’ goals and preferences. They also provide patient education and support (112). A systematic review concluded that such models reduce breathlessness intensity and depression in patients with advanced disease with no observable effect on HRQOL, and mixed evidence around function (60). Another single-blind RCT showed significant improvements in mastery and HRQOL in favor of the intervention group but not in symptom scores (113). A single-blind RCT of patients with advanced respiratory conditions randomized to receive this type of care showed improved breathlessness mastery and possibly survival in subgroup of COPD and ILD patients (59). Qualitative analysis suggested that such models not only improved CB care but also improved patient confidence, control and dignity due to their holistic approach (114). A similar outpatient-based care model for F-ILD patients that integrated symptom management with routine care at visits every 6 weeks showed reduced CB burden and depression at the 12-month mark (77). A home-based care model led by a PC nurse who facilitated case conference for advanced ILD patients was also associated with improved PC outcomes, HRQOL, and anxiety and depression, but breathlessness was not assessed independently (115). This model employed a PC nurse who performed home visits, identified needs, created an interdisciplinary care plan and collaborated with allied staff to ensure care delivery. Outside of clinical trials access to such services is limited but there are a few real-world practices where the therapeutic strategies used in these models have been successfully integrated into routine care (74,104,116,117).

Proposed patient-centered CB management approach in F-ILD

The proposed stepwise approach tailors NPI, oxygen and opioids in response to various CB grades (mild, moderate and severe) based on dyspnea severity scores with rest, activities, ADL impairment and hypoxemia. It also addresses symptom crises (context and control domains of dyspnea) and caregiver concerns from diagnosis to EoL. This approach is informed by holistic CB assessment that relies on narrative enquiry along with the use of CB measurement tool (Figure 5) (101). The proposed management approach addresses gaps in CB care by focusing on early and personalized implementation of various types of NPIs that are not commonly considered in outpatient CB assessments. All interventions are guided by patient goals and contexts. Early assessments for exertional hypoxemia guide the use of oxygen for exertional then resting dyspnea as disease progresses. Opioids are added for worsening dyspnea and functional impairments only after optimization of all other therapies. Thus, emphasizing personalized timing and sequence of CB therapies (101,118).

Figure 5 Proposed stepwise chronic dyspnea management in interstitial lung diseases. a, education about diet, staying active, medications; recognizing symptom crises and required/appropriate response; monitoring of oxygen saturation, chest infection and heart failure; b, includes allied health, primary care, personal care workers and assessment of need for wheelchair, urinal, commode, hospital beds, wedge pillow, transfer lift for home rehabilitation strategies. Adapted from (101). NRS, numeric rating scale; ADL, activities of daily living; WW, wheeled walker.

The key to personalization of therapies is the use of Edmonton Dyspnea Inventory, patient reported dyspnea outcome measure, and a narrative approach to identify patient and carer needs, goals and prioritize actions (Figure 4) (30). Assessment based on these parameters is helpful to identify and triage patients appropriately. For example, patients with resting dyspnea and/or dyspnea with minimal activities like talking, eating, bathing etc. are at high risk of hospitalization (119,120). Therefore, urgent interventions may be beneficial in such cases. The use of this tool facilitates recognition of high-risk patients and the algorithm directs clinician to the most appropriate actions in a stepwise fashion. NPI are foundational to CB care and their success is predicated on patient engagement in the process. Therefore, NPI choice should be guided by patient goals, preferences, motivation and ability. Thus, clinicians should ascertain patient goals and preferences as the first step and review patient expectations whenever new interventions are applied. The goals of therapy are to minimize breathlessness distress and enable a better HRQOL as total resolution of CB may not be possible. Clarifying goals and reviewing expectations creates a shared understanding that is essential to success. In addition to formal PR program referral, other strategies like activity, behavior and environmental modifications are considered in a step-wise fashion as outlined in Figure 5. These NPI address patient need for practical and personalized advice to improve their “feel and function” (121). Self-management education can help patients understand CB, its triggers, recognize crises, how to manage and avoid these, how to become intentional and confident in the use of NPI, oxygen and medications. This facilitates adaptive coping. Caregiver needs should be reviewed and addressed at all stages when possible; their ongoing input is helpful to assess response to various therapies. Given chronicity many patients may downplay symptoms, or not fully appreciate impact that may be easily noticed by the caregiver instead.

With the onset of severe CB, worsening ADL impairments and respiratory failure patients will need more frequent follow up at shorter intervals. Home-based allied support may be beneficial in such cases to frequently assess oxygen needs and titrate oxygen rather than waiting for clinic appointments. Use of walking aids, wheelchairs and oxygen strollers can help reduce dyspnea distress, and oxygen needs by reducing metabolic demands during various activities and should be considered early and reassessed with progressive needs. When patients approach EoL and prefer care at home, in home-supports such as a hospital beds, wedge pillows, transfer lifts, bedside commode and urinals can be considered. Once NPI and oxygen are optimized, opioids can be considered in patients with severe CB with rest, minimal exertion, frequent crisis and/or impaired ADL. Low dose opioids, short-acting formulations are preferred to allow easy and frequent titrations. Scheduled and pre-emptive dosing can be considered for exertional or anticipated CB. Both oral and transmucosal routes can be beneficial as needed, the latter for more immediate effect as desired in a crisis situation (100). Providing written action plans are helpful to patients, their carers and other members of the care team so patients know what to do and who to call for support and additionally, consistent support and instructions can be provided to them by their home care team whenever needed (45). Early evidence from retrospective studies suggests many benefits including better care, improved symptoms, patients and carer confidence, preparedness and ability to cope (45,104,122). This approach is also associated with reduced hospitalizations and costs at EoL in F-ILD (123).

Limitations and strengths

The review has limitations. First, a systematic literature search was not undertaken, though efforts were made to provide most current and relevant information. A comprehensive review of all available CB assessment tools and CB management was not addressed here. This was deemed beyond the scope of this paper. Second, CB was explored in the context of F-ILD including IPF and other types of ILD depending on the available data. It is important to acknowledge that CB trajectories may vary based on the underlying ILD etiology. Lastly, this review serves as a summary of significant findings from original research studies.

Future directions

A comprehensive strategy is crucial for transforming breathlessness management in F-ILD. This involves increasing public and healthcare system awareness, enhancing clinician knowledge and competency, and fostering a holistic practice culture for CB care. Knowledge dissemination is needed for urgent translation of existing best practices. This should address systematic CB screening and assessment, prioritizing implementation of NPI, oxygen, opioids along with patient education. Access to home supports based on available resources is beneficial to patients and carers. Future efforts must also focus on high-quality research to inform integration of CB assessment and management. Many NPIs, prevalent in practice are derived from physiotherapy and occupational therapy literature and require further exploration in medical domain. Similarly, research on opioids is required to guide patient selection and prescribing. RCTs for many CB interventions (opioids, NPI) have proven challenging; trial populations are heterogenous with varying CB severity levels and impairments. In contrast real-world practice suggests benefits of various interventions in narrowly defined populations suggesting the need for careful consideration of inclusion criteria for participant recruitment. A better understanding of factors determining intervention responsiveness may lead to more refined inclusion criteria, increasing the likelihood of positive results and greater confidence in such results. However, this may necessitate larger and longer trials to accrue such a defined population in F-ILD. Assembling a researcher collaborative for prioritizing and standardizing meaningful outcomes for research, defining non-PR NPI, and supporting efforts to facilitate impactful research could be beneficial. Similar efforts in F-ILD have borne fruit.

Development and evaluation of self-management education for CB is also awaited, along with study of wearable devices, digital applications and remote monitoring tools. These technologies can map the trajectory of dyspnea, patient needs, and usage in real-world settings, potentially enhancing care (124). Given the inherent complexity of CB interventions, development and validation of clinical decision supports or algorithms similar to the described approach can empower clinicians in improving CB assessment and management (Figure 5). Evidence suggests that using validated management tools can lead to better care (125).

Conclusions

CB is prevalent in F-ILD causing considerable health-related suffering in patients and adding to caregiver burden. To ensure comprehensive care for ILD, clinicians need to actively identify, assess, treat CB, and, where possible, prevent crises. A proactive approach involves screening for CB and utilizing validated tools within a holistic narrative framework of assessment. The assessment aims to guide personalized CB management through four steps. First, optimizing disease-specific ILD treatments, including immunosuppressants, biologics, and anti-fibrotic agents. Second, implementing single or multicomponent NPI as the foundational step. Third, effectively using oxygen for exertional and resting hypoxemia. Finally, introducing opioids after sequential optimization of NPI and oxygen. Despite existing guidelines, decisions on CB therapies often hinge on provider preference or comfort and institutional practice cultures rather than careful consideration of patient-specific factors, existing evidence and common-sense. This hinders care as many providers shy away from CB. A commitment to changing clinician behaviors and shifting practice culture from disease-based to patient-centered will not only enhance patient and family lives but also benefit healthcare providers.

Acknowledgments

The author expresses gratitude to ILD patients and their families, Kaye Edmonton Clinic—ILD clinic staff, Dr. Janice Richman-Eisenstat, and many colleagues around the world who inspire her to carry on when things get tough.

Funding: None.

Footnote

Peer Review File: Available at https://apm.amegroups.com/article/view/10.21037/apm-24-7/prf

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://apm.amegroups.com/article/view/10.21037/apm-24-7/coif). The author reports grants from University Hospital Foundation, Alberta Health Services-SCN and Boehringer-Ingelheim in the past 3 years; and speaker fees from Boehringer-Ingelheim for lectures. The author has no other conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Wijsenbeek M, Cottin V. Spectrum of Fibrotic Lung Diseases. N Engl J Med 2020;383:958-68. [Crossref] [PubMed]
2. Johnson MJ, Yorke J, Hansen-Flaschen J, et al. Towards an expert consensus to delineate a clinical syndrome of chronic breathlessness. Eur Respir J 2017;49:1602277. [Crossref] [PubMed]
3. Carvajalino S, Reigada C, Johnson MJ, et al. Symptom prevalence of patients with fibrotic interstitial lung disease: a systematic literature review. BMC Pulm Med 2018;18:78. [Crossref] [PubMed]
4. Ryerson CJ, Donesky D, Pantilat SZ, et al. Dyspnea in idiopathic pulmonary fibrosis: a systematic review. J Pain Symptom Manage 2012;43:771-82. [Crossref] [PubMed]
5. Nishiyama O, Taniguchi H, Kondoh Y, et al. A simple assessment of dyspnoea as a prognostic indicator in idiopathic pulmonary fibrosis. Eur Respir J 2010;36:1067-72. [Crossref] [PubMed]
6. Araki T, Katsura H, Sawabe M, et al. A clinical study of idiopathic pulmonary fibrosis based on autopsy studies in elderly patients. Intern Med 2003;42:483-9. [Crossref] [PubMed]
7. Rudilla D, Beceiro MJ, Alonso T, et al. Psychological Profile of Patients Diagnosed With Idiopathic Pulmonary Fibrosis. Arch Bronconeumol 2022;58:191-3. [Crossref] [PubMed]
8. Swigris JJ, Kuschner WG, Jacobs SS, et al. Health-related quality of life in patients with idiopathic pulmonary fibrosis: a systematic review. Thorax 2005;60:588-94. [Crossref] [PubMed]
9. Rautajoki T, Lehto JT, Sutinen E, et al. Dyspnea Associates With a Widely Impaired Quality of Life in Idiopathic Pulmonary Fibrosis Patients: A Longitudinal Study Using 15D. J Palliat Med 2023;26:1357-64. [Crossref] [PubMed]
10. Kreuter M, Swigris J, Pittrow D, et al. The clinical course of idiopathic pulmonary fibrosis and its association to quality of life over time: longitudinal data from the INSIGHTS-IPF registry. Respir Res 2019;20:59. [Crossref] [PubMed]
11. Collard HR, Chen SY, Yeh WS, et al. Health care utilization and costs of idiopathic pulmonary fibrosis in U.S. Medicare beneficiaries aged 65 years and older. Ann Am Thorac Soc 2015;12:981-7. [Crossref] [PubMed]
12. Rajala K, Lehto JT, Saarinen M, et al. End-of-life care of patients with idiopathic pulmonary fibrosis. BMC Palliat Care 2016;15:85. [Crossref] [PubMed]
13. Kochovska S, Chang S, Ferreira D, et al. Invisibility of breathlessness in clinical consultations: a cross-sectional, national online survey. Eur Respir J 2022;60:2201603. [Crossref] [PubMed]
14. Bausewein C, Booth S, Gysels M, et al. Non-pharmacological interventions for breathlessness in advanced stages of malignant and non-malignant diseases. Cochrane Database Syst Rev 2008;CD005623. [PubMed]
15. Barnes H, McDonald J, Smallwood N, et al. Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database Syst Rev 2016;3:CD011008. [Crossref] [PubMed]
16. Currow DC, Abernethy AP, Ko DN. The active identification and management of chronic refractory breathlessness is a human right. Thorax 2014;69:393-4. [Crossref] [PubMed]
17. Raghu G, Remy-Jardin M, Richeldi L, et al. Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2022;205:e18-47. [Crossref] [PubMed]
18. Janssen DJA, Bajwah S, Boon MH, et al. European Respiratory Society clinical practice guideline: palliative care for people with COPD or interstitial lung disease. Eur Respir J 2023;62:2202014. [Crossref] [PubMed]
19. Sullivan DR, Iyer AS, Enguidanos S, et al. Palliative Care Early in the Care Continuum among Patients with Serious Respiratory Illness: An Official ATS/AAHPM/HPNA/SWHPN Policy Statement. Am J Respir Crit Care Med 2022;206:e44-69. [Crossref] [PubMed]
20. Kim JW, Atkins C, Wilson AM. Barriers to specialist palliative care in interstitial lung disease: a systematic review. BMJ Support Palliat Care 2019;9:130-8. [Crossref] [PubMed]
21. Kreuter M, Bendstrup E, Russell AM, et al. Palliative care in interstitial lung disease: living well. Lancet Respir Med 2017;5:968-80. [Crossref] [PubMed]
22. Krajnik M, Hepgul N, Wilcock A, et al. Do guidelines influence breathlessness management in advanced lung diseases? A multinational survey of respiratory medicine and palliative care physicians. BMC Pulm Med 2022;22:41. [Crossref] [PubMed]
23. Bajwah S, Higginson IJ, Ross JR, et al. Specialist palliative care is more than drugs: a retrospective study of ILD patients. Lung 2012;190:215-20. [Crossref] [PubMed]
24. Lindell KO, Liang Z, Hoffman LA, et al. Palliative care and location of death in decedents with idiopathic pulmonary fibrosis. Chest 2015;147:423-9. [Crossref] [PubMed]
25. Lovell N, Etkind SN, Bajwah S, et al. Control and Context Are Central for People With Advanced Illness Experiencing Breathlessness: A Systematic Review and Thematic Synthesis. J Pain Symptom Manage 2019;57:140-155.e2. [Crossref] [PubMed]
26. Lemmers JMJ, Vonk MC, van den Ende CHM. Patient-reported outcomes to assess dyspnoea in interstitial lung disease and pulmonary hypertension: a systematic literature review of measurement properties. Eur Respir Rev 2022;31:220091. [Crossref] [PubMed]
27. Elliott-Button HL, Johnson MJ, Nwulu U, et al. Identification and Assessment of Breathlessness in Clinical Practice: A Systematic Review and Narrative Synthesis. J Pain Symptom Manage 2020;59:724-733.e19. [Crossref] [PubMed]
28. Sunjaya A, Poulos L, Reddel H, et al. Qualitative validation of the modified Medical Research Council (mMRC) dyspnoea scale as a patient-reported measure of breathlessness severity. Respir Med 2022;203:106984. [Crossref] [PubMed]
29. Perez T, Roche N, Nunes H, et al. Dyspnea-induced Limitation (DYSLIM), a new self-administered concise questionnaire to evaluate dyspnea-related activity limitation in chronic respiratory diseases. Respir Med 2023;217:107309. [Crossref] [PubMed]
30. Kalluri M, Cui Y, Wang T, et al. Validation of a Novel Clinical Dyspnea Scale - A Retrospective Pilot Study. Am J Hosp Palliat Care 2024;41:253-61. [Crossref] [PubMed]
31. Carel H, Macnaughton J, Dodd J. Invisible suffering: breathlessness in and beyond the clinic. Lancet Respir Med 2015;3:278-9. [Crossref] [PubMed]
32. Banzett RBB, Sheridan AR, Baker KM, et al. 'Scared to death' dyspnoea from the hospitalised patient's perspective. BMJ Open Respir Res 2020;7:e000493. [Crossref] [PubMed]
33. Sunjaya A, Martin A, Arnott C, et al. "It's like a forgotten issue sometimes …": Qualitative study of individuals living and caring for people with chronic breathlessness. Clin Respir J 2023;17:694-700. [Crossref] [PubMed]
34. Lee JYT, Tikellis G, Corte TJ, et al. The supportive care needs of people living with pulmonary fibrosis and their caregivers: a systematic review. Eur Respir Rev 2020;29:190125. [Crossref] [PubMed]
35. Wijsenbeek M, Molina-Molina M, Chassany O, et al. Developing a conceptual model of symptoms and impacts in progressive fibrosing interstitial lung disease to evaluate patient-reported outcome measures. ERJ Open Res 2022;8:00681-2021. [Crossref] [PubMed]
36. 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:S98-106. [Crossref] [PubMed]
37. Bajwah S, Higginson IJ, Ross JR, et al. The palliative care needs for fibrotic interstitial lung disease: a qualitative study of patients, informal caregivers and health professionals. Palliat Med 2013;27:869-76. [Crossref] [PubMed]
38. Mahler DA, Selecky PA, Harrod CG, et al. American College of Chest Physicians consensus statement on the management of dyspnea in patients with advanced lung or heart disease. Chest 2010;137:674-91. [Crossref] [PubMed]
39. Ferreira DH, Kochovska S, Brunelli VN, et al. Understanding persistent breathlessness: impact on patients and optimal approaches to symptomatic reduction - an overview. Expert Rev Respir Med 2023;17:365-79. [Crossref] [PubMed]
40. Khor YH, Cottin V, Holland AE, et al. Treatable traits: a comprehensive precision medicine approach in interstitial lung disease. Eur Respir J 2023;62:2300404. [Crossref] [PubMed]
41. Dowman L, Hill CJ, May A, et al. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev 2021;2:CD006322. [PubMed]
42. Rochester CL, Alison JA, Carlin B, et al. Pulmonary Rehabilitation for Adults with Chronic Respiratory Disease: An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2023;208:e7-e26. [Crossref] [PubMed]
43. Khor YH, Saravanan K, Holland AE, et al. A mixed-methods pilot study of handheld fan for breathlessness in interstitial lung disease. Sci Rep 2021;11:6874. [Crossref] [PubMed]
44. Parisien-La Salle S, Abel Rivest E, Boucher VG, et al. Effects of Pursed Lip Breathing on Exercise Capacity and Dyspnea in Patients With Interstitial Lung Disease: A RANDOMIZED, CROSSOVER STUDY. J Cardiopulm Rehabil Prev 2019;39:112-7. [Crossref] [PubMed]
45. Kalluri M, Younus S, Archibald N, et al. Action plans in idiopathic pulmonary fibrosis: a qualitative study-'I do what I can do'. BMJ Support Palliat Care 2021; Epub ahead of print. [Crossref] [PubMed]
46. Wright C, Hart SP, Sykes D, et al. A feasibility, wait-list design randomised controlled trial of a complex breathlessness intervention in idiopathic pulmonary fibrosis (BREEZE-IPF). Eur Respir J 2023;62:OA2587.
47. van Manen MJG, van 't Spijker A, Tak NC, et al. Patient and partner empowerment programme for idiopathic pulmonary fibrosis. Eur Respir J 2017;49:1601596. [Crossref] [PubMed]
48. Reilly CC, Maddocks M, Chalder T, et al. A randomised, controlled, feasibility trial of an online, self-guided breathlessness supportive intervention (SELF-BREATHE) for individuals with chronic breathlessness due to advanced disease. ERJ Open Res 2023;9:00508-2022. [Crossref] [PubMed]
49. Corte T. REBUILD-SM: A Randomised Clinical Trial of a Digital Self-management Package for People With Interstitial Lung Disease. Accessed 3 January 2024. Available online: https://clinicaltrials.gov/study/NCT06122233?cond=IPF,%20ILD&term=DYSPNEA&intr=DIGITAL%20APPLICATIONS&rank=1#study-overview
50. Kreuter M, Wasmuth L, Kotzerke M, et al. Yoga in patients with fibrosing interstitial lung diseases – a feasibility trial. Eur Respir J 2020;56:773.
51. Moderno EV, Yamaguti WP, Schettino GP, et al. Effects of proportional assisted ventilation on exercise performance in idiopathic pulmonary fibrosis patients. Respir Med 2010;104:134-41. [Crossref] [PubMed]
52. Sanguanwong N, Jantarangsi N, Ngeyvijit J, et al. Effect of noninvasive respiratory support on interstitial lung disease with acute respiratory failure: A systematic review and meta-analysis. Can J Respir Ther 2023;59:232-44. [Crossref] [PubMed]
53. Faverio P, De Giacomi F, Bonaiti G, et al. Management of Chronic Respiratory Failure in Interstitial Lung Diseases: Overview and Clinical Insights. Int J Med Sci 2019;16:967-80. [Crossref] [PubMed]
54. Visca D, Mori L, Tsipouri V, et al. Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial. Lancet Respir Med 2018;6:759-70. [Crossref] [PubMed]
55. Bell EC, Cox NS, Goh N, et al. Oxygen therapy for interstitial lung disease: a systematic review. Eur Respir Rev 2017;26:160080. [Crossref] [PubMed]
56. Jacobs SS, Krishnan JA, Lederer DJ, et al. Home Oxygen Therapy for Adults with Chronic Lung Disease. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 2020;202:e121-41. [Crossref] [PubMed]
57. Weinreich UM, Burchardt C, Huremovic J. The effect of domiciliary high flow nasal cannula treatment on dyspnea and walking distance in patients with interstitial lung disease - A pilot study. Chron Respir Dis 2022;19:14799731221137085. [Crossref] [PubMed]
58. Al Chikhanie Y, Veale D, Verges S, et al. The effect of heated humidified nasal high flow oxygen supply on exercise tolerance in patients with interstitial lung disease: A pilot study. Respir Med 2021;186:106523. [Crossref] [PubMed]
59. Higginson IJ, Bausewein C, Reilly CC, et al. An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial. Lancet Respir Med 2014;2:979-87. [Crossref] [PubMed]
60. Brighton LJ, Miller S, Farquhar M, et al. Holistic services for people with advanced disease and chronic breathlessness: a systematic review and meta-analysis. Thorax 2019;74:270-81. [Crossref] [PubMed]
61. Matsuda Y, Morita T, Miyaji T, et al. Morphine for Refractory Dyspnea in Interstitial Lung Disease: A Phase I Study (JORTC-PAL 05). J Palliat Med 2018;21:1718-23. [Crossref] [PubMed]
62. Polosa R, Simidchiev A, Walters EH. Nebulised morphine for severe interstitial lung disease. Cochrane Database Syst Rev 2002;2002:CD002872. [Crossref] [PubMed]
63. Kronborg-White S, Andersen CU, Kohberg C, et al. Palliation of chronic breathlessness with morphine in patients with fibrotic interstitial lung disease - a randomised placebo-controlled trial. Respir Res 2020;21:195. [Crossref] [PubMed]
64. Ferreira DH, Ekström M, Bajwah S, et al. Regular, low-dose, sustained-release morphine for persisting breathlessness in interstitial lung disease: a randomised, double-blind, placebo-controlled, crossover trial. Eur Respir J 2023;62:2300702. [Crossref] [PubMed]
65. Bajwah S, Davies JM, Tanash H, et al. Safety of benzodiazepines and opioids in interstitial lung disease: a national prospective study. Eur Respir J 2018;52:1801278. [Crossref] [PubMed]
66. Simon ST, Higginson IJ, Booth S, et al. Benzodiazepines for the relief of breathlessness in advanced malignant and non-malignant diseases in adults. Cochrane Database Syst Rev 2010;CD007354. [PubMed]
67. Higginson IJ, Wilcock A, Johnson MJ, et al. Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility). Thorax 2020;75:176-9. [PubMed]
68. Currow DC, Ekström M, Louw S, et al. Sertraline in symptomatic chronic breathlessness: a double blind, randomised trial. Eur Respir J 2019;53:1801270. [Crossref] [PubMed]
69. Kanezaki M, Terada K, Ebihara S. Nasal stimulation with l-menthol ameliorates breathlessness in patients with interstitial lung disease. Eur Respir J 2023;61:2202453. [Crossref] [PubMed]
70. Yates P, Zhao I. Update on complex nonpharmacological interventions for breathlessness. Curr Opin Support Palliat Care 2012;6:144-52. [Crossref] [PubMed]
71. Booth S, Moffat C, Burkin J, et al. Nonpharmacological interventions for breathlessness. Curr Opin Support Palliat Care 2011;5:77-86. [Crossref] [PubMed]
72. Gupta A, Sedhom R, Sharma R, et al. Nonpharmacological Interventions for Managing Breathlessness in Patients With Advanced Cancer: A Systematic Review. JAMA Oncol 2021;7:290-8. [Crossref] [PubMed]
73. Ahmadi Z, Sandberg J, Shannon-Honson A, et al. Is chronic breathlessness less recognised and treated compared with chronic pain? A case-based randomised controlled trial. Eur Respir J 2018;52:1800887. [Crossref] [PubMed]
74. Younus S, Bakal JA, Richman-Eisenstat J, et al. Comparison of Palliative Care Models in Idiopathic Pulmonary Fibrosis. Appl Sci 2021;11:9028. [Crossref]
75. Hoffman M, Mellerick C, Symons K, et al. Pulmonary rehabilitation for interstitial lung disease: Referral and patient experiences. Chron Respir Dis 2021;18:14799731211046022. [Crossref] [PubMed]
76. Duke JD, Moua T, Ridgeway JL, et al. Home-Based Pulmonary Rehabilitation and Health Coaching in Fibrotic Interstitial Lung Disease: Implementation and Qualitative Assessment of a Pilot Telehealth Program. J Cardiopulm Rehabil Prev 2023;43:270-6. [Crossref] [PubMed]
77. Bassi I, Guerrieri A, Carpano M, et al. Feasibility and efficacy of a multidisciplinary palliative approach in patients with advanced interstitial lung disease. A pilot randomised controlled trial. Pulmonology 2023;29:S54-62. [Crossref] [PubMed]
78. Luckett T, Phillips J, Johnson MJ, et al. Contributions of a hand-held fan to self-management of chronic breathlessness. Eur Respir J 2017;50:1700262. [Crossref] [PubMed]
79. Brew A, O'Beirne S, Johnson MJ, et al. Airflow rates and breathlessness recovery from submaximal exercise in healthy adults: prospective, randomised, cross-over study. BMJ Support Palliat Care 2023;spcare-2023-004309.
80. Qian MYY, Politis J, Thompson M, et al. Individualized breathlessness interventions may improve outcomes in patients with advanced COPD. Respirology 2018;23:1146-51. [Crossref] [PubMed]
81. Christenbery TL. Dyspnea self-management strategies: use and effectiveness as reported by patients with chronic obstructive pulmonary disease. Heart Lung 2005;34:406-14. [Crossref] [PubMed]
82. Nishiyama O, Taniguchi H, Kondoh Y, et al. Dyspnoea at 6-min walk test in idiopathic pulmonary fibrosis: comparison with COPD. Respir Med 2007;101:833-8. [Crossref] [PubMed]
83. Khor YH, Gutman L, Abu Hussein N, et al. Incidence and Prognostic Significance of Hypoxemia in Fibrotic Interstitial Lung Disease: An International Cohort Study. Chest 2021;160:994-1005. [Crossref] [PubMed]
84. Ley B, Collard HR, King TE Jr. Clinical course and prediction of survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011;183:431-40. [Crossref] [PubMed]
85. Branson RD. Portable Oxygen Concentrators: Caveat Emptor. Respir Care 2023;68:547-8. [Crossref] [PubMed]
86. 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. [Crossref] [PubMed]
87. Ora J, Coppola A, Perduno A, et al. Acute effect of oxygen therapy on exercise tolerance and dyspnea perception in ILD patients. Monaldi Arch Chest Dis 2021;92: [Crossref] [PubMed]
88. Tikellis G, Hoffman M, Mellerick C, et al. Barriers to and facilitators of the use of oxygen therapy in people living with an interstitial lung disease: a systematic review of qualitative evidence. Eur Respir Rev 2023;32:230066. [Crossref] [PubMed]
89. Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011;183:788-824. [Crossref] [PubMed]
90. Lim RK, Humphreys C, Morisset J, et al. Oxygen in patients with fibrotic interstitial lung disease: an international Delphi survey. Eur Respir J 2019;54:1900421. [Crossref] [PubMed]
91. Saleem F, Ryerson CJ, Sarma N, et al. Predicting New-onset Exertional and Resting Hypoxemia in Fibrotic Interstitial Lung Disease. Ann Am Thorac Soc 2023;20:1726-34. [Crossref] [PubMed]
92. Alfieri V, Crisafulli E, Visca D, et al. Physiological predictors of exertional oxygen desaturation in patients with fibrotic interstitial lung disease. Eur Respir J 2020;55:1901681. [Crossref] [PubMed]
93. Clark KP, Degenholtz HB, Lindell KO, et al. Supplemental Oxygen Therapy in Interstitial Lung Disease: A Narrative Review. Ann Am Thorac Soc 2023;20:1541-9. [Crossref] [PubMed]
94. Casaburi R, Hess M, Porszasz J, et al. Evaluation of Over-the-Counter Portable Oxygen Concentrators Utilizing a Metabolic Simulator. Respir Care 2023;68:445-51. [Crossref] [PubMed]
95. Spece LJ, Epler EM, Duan K, et al. Reassessment of Home Oxygen Prescription after Hospitalization for Chronic Obstructive Pulmonary Disease. A Potential Target for Deimplementation. Ann Am Thorac Soc 2021;18:426-32. [Crossref] [PubMed]
96. Du Plessis JP, Fernandes S, Jamal R, et al. Exertional hypoxemia is more severe in fibrotic interstitial lung disease than in COPD. Respirology 2018;23:392-8. [Crossref] [PubMed]
97. Kalluri M, Watanabe SM, Burton-MacLeod S. Letter to the Editor: Together We Are Better in Interstitial Lung Disease and Palliative Care: A Collaborative Approach to Meet Care Needs and Improve Education. Journal of Palliative Medicine 2024;27:156-7.
98. Kalluri M, Richman-Eisenstat J. Breathing is not an option; dyspnea is. J Palliat Care 2014;30:188-91. [Crossref] [PubMed]
99. Kalluri M, Richman-Eisenstat J. Early and Integrated Palliative Care to Achieve a Home Death in Idiopathic Pulmonary Fibrosis. J Pain Symptom Manage 2017;53:1111-5. [Crossref] [PubMed]
100. Fong S, Richman-Eisenstat J, Kalluri M. Buccal Hydromorphone Syrup for Managing Dyspnea in Idiopathic Pulmonary Fibrosis. Am J Hosp Palliat Care 2021;38:1046-52. [Crossref] [PubMed]
101. Kalluri Meena MS, Richman-Eisenstat J, Ferrara G, et al. Opioids for dyspnea in ILD: Does the sequence and timing of therapy matter? European Respiratory Journal 2024; [Crossref]
102. Ferreira DH, Ekström M, Verberkt C, et al. Is being able to walk to the letterbox life-changing? A qualitative assessment of measures of improvement in persistent breathlessness. ERJ Open Res 2023;9:00530-2022. [Crossref] [PubMed]
103. Chen X, Treanor D, Le B, et al. Gaps in Opioid Prescription for Severe Breathlessness in Hospitalized Patients With Chronic Obstructive Pulmonary Disease or Interstitial Lung Disease. J Pain Symptom Manage 2020;60:e36-9. [Crossref] [PubMed]
104. Pooler C, Richman-Eisenstat J, Kalluri M. Early integrated palliative approach for idiopathic pulmonary fibrosis: A narrative study of bereaved caregivers' experiences. Palliat Med 2018;32:1455-64. [Crossref] [PubMed]
105. Date K, Williams B, Cohen J, et al. Modified-release morphine or placebo for chronic breathlessness: the MABEL trial protocol. ERJ Open Res 2023;9:00167-2023. [Crossref] [PubMed]
106. Ekström M, Janssen DJA. Should opioids be used for breathlessness and in whom? A PRO and CON debate of the evidence. Curr Opin Support Palliat Care 2023;17:263-9. [Crossref] [PubMed]
107. Ferreira DH, Silva JP, Quinn S, et al. Blinded Patient Preference for Morphine Compared to Placebo in the Setting of Chronic Refractory Breathlessness--An Exploratory Study. J Pain Symptom Manage 2016;51:247-54. [Crossref] [PubMed]
108. Smallwood N, Mann J, Guo H, et al. Patients With Fibrotic Interstitial Lung Disease Receive Supportive and Palliative Care Just Prior to Death. Am J Hosp Palliat Care 2021;38:154-60. [Crossref] [PubMed]
109. Vozoris NT. Prescription opioid use in advanced COPD: benefits, perils and controversies. Eur Respir J 2017;49:1700479. [Crossref] [PubMed]
110. Marciniuk DD, Goodridge D, Hernandez P, et al. Managing dyspnea in patients with advanced chronic obstructive pulmonary disease: a Canadian Thoracic Society clinical practice guideline. Can Respir J 2011;18:69-78. [Crossref] [PubMed]
111. Liu M, Xiao W, Du L, et al. Effectiveness and safety of opioids on breathlessness and exercise endurance in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis of randomised controlled trials. Palliat Med 2023;37:1365-78. [Crossref] [PubMed]
112. Bausewein C, Jolley C, Reilly C, et al. Development, effectiveness and cost-effectiveness of a new out-patient Breathlessness Support Service: study protocol of a phase III fast-track randomised controlled trial. BMC Pulm Med 2012;12:58. [Crossref] [PubMed]
113. Schunk M, Le L, Syunyaeva Z, et al. Effectiveness of a specialised breathlessness service for patients with advanced disease in Germany: a pragmatic fast-track randomised controlled trial (BreathEase). Eur Respir J 2021;58:2002139. [Crossref] [PubMed]
114. Gysels M, Reilly CC, Jolley CJ, et al. Dignity Through Integrated Symptom Management: Lessons From the Breathlessness Support Service. J Pain Symptom Manage 2016;52:515-24. [Crossref] [PubMed]
115. Bajwah S, Ross JR, Wells AU, et al. Palliative care for patients with advanced fibrotic lung disease: a randomised controlled phase II and feasibility trial of a community case conference intervention. Thorax 2015;70:830-9. [Crossref] [PubMed]
116. Bausewein C, Schunk M, Schumacher P, et al. Breathlessness services as a new model of support for patients with respiratory disease. Chron Respir Dis 2018;15:48-59. [Crossref] [PubMed]
117. Smallwood N, Thompson M, Warrender-Sparkes M, et al. Integrated respiratory and palliative care may improve outcomes in advanced lung disease. ERJ Open Res 2018;4:00102-2017. [Crossref] [PubMed]
118. van den Bosch L, Wang T, Bakal JA, et al. A Retrospective, Descriptive Study of Dyspnea Management in a Multidisciplinary Interstitial Lung Disease Clinic. Am J Hosp Palliat Care 2023;40:153-63. [Crossref] [PubMed]
119. Stevens JP, Dechen T, Schwartzstein RM, et al. Association of dyspnoea, mortality and resource use in hospitalised patients. Eur Respir J 2021;58:1902107. [Crossref] [PubMed]
120. Stevens JP, Sheridan AR, Bernstein HB, et al. A Multidimensional Profile of Dyspnea in Hospitalized Patients. Chest 2019;156:507-17. [Crossref] [PubMed]
121. Lin D, Borjan M, San Andres SD, et al. The Role of PT, OT, and Other Therapies in Palliative Care for Seriously Ill Patients. In: Ferrell BR, Paice JA. Editors. Oxford Textbook of Palliative Nursing. 2019.
122. Kalluri M, Claveria F, Ainsley E, et al. Beyond Idiopathic Pulmonary Fibrosis Diagnosis: Multidisciplinary Care With an Early Integrated Palliative Approach Is Associated With a Decrease in Acute Care Utilization and Hospital Deaths. J Pain Symptom Manage 2018;55:420-6. [Crossref] [PubMed]
123. Kalluri M, Lu-Song J, Younus S, et al. Health Care Costs at the End of Life for Patients with Idiopathic Pulmonary Fibrosis. Evaluation of a Pilot Multidisciplinary Collaborative Interstitial Lung Disease Clinic. Ann Am Thorac Soc 2020;17:706-13. [Crossref] [PubMed]
124. Nakshbandi G, Moor CC, Wijsenbeek MS. Role of the internet of medical things in care for patients with interstitial lung disease. Curr Opin Pulm Med 2023;29:285-92. [Crossref] [PubMed]
125. Sunjaya AP, Homaira N, Corcoran K, et al. Assessment and diagnosis of chronic dyspnoea: a literature review. NPJ Prim Care Respir Med 2022;32:10. [Crossref] [PubMed]