Pulmonary care for ALS: Progress, gaps, and paths forward

Abstract

Introduction:

Adults with amyotrophic lateral sclerosis (ALS) have been using home mechanical ventilation for over 50 years. More recently, home respiratory care has evolved to include portable home ventilators, airway clearance devices, and physiological assessments with telemonitoring capability.

Current State of Respiratory Care:

National organizations currently offer incentives for providing a pulmonary care specialist within a multidisciplinary ALS clinic; however, several critical gaps exist between the available technology and employing a clinician with the necessary expertise.

Gaps in Care:

Lack of formal training and poor financial incentives have led to a paucity of both clinicians and active clinical research engaging in the home respiratory care of ALS. Criteria for noninvasive ventilation (NIV) initiation are controversial, and few guidelines exist on the ideal subsequent adjustments of NIV with evolving disease. Consequently, many patients with ALS tolerate NIV poorly and must face the harrowing decision of hospice vs tracheostomy. Advancement of respiratory care in ALS has been hindered by critical gaps in pulmonologist availability, training in chronic respiratory failure, financial support, clinical research, and clarity on ventilation management beyond initiation.

Bringing Respiratory Care Up to Speed:

Only a multifaceted approach will suffice for addressing the voids in ALS respiratory care, including various education initiatives, financial incentives, clinical research programs, and elevating the standard of respiratory care.

1 ∣. INTRODUCTION

People with amyotrophic lateral sclerosis (ALS) have used home mechanical ventilation since at least the 1970s.¹ After a landmark trial demonstrated the survival benefit of noninvasive ventilation (NIV),² radical technological developments have improved clinicians’ ability to optimize home respiratory care of neuromuscular disease. The ability to leverage this technology has given rise to a new pulmonary subspeciality focused on outpatient management of chronic respiratory failure. Canada, Western Europe, and other developed countries have mastered this approach and published their own guidelines.^3-5 Unfortunately, these technological advancements have outpaced medical education for pulmonary physicians in the United States.

Consequently, ALS centers in the United States may lack a dedicated physician capable of delivering an evolving respiratory care plan alongside disease progression. Geographic location may strongly influence patient access to a variety of respiratory devices, airway clearance regimens, telemonitoring capability, and clinical research participation. Instead, many patients may be asked to decide on hospice vs tracheostomy upon any discomfort with NIV. The gap between possibility and reality has charged opinions on the state of respiratory care in ALS.⁶

The purpose of this review is to expand upon previous commentary on this topic by highlighting the history of ALS respiratory care, describing its current state, identifying critical practice gaps, and proposing several paths forward for the United States medical system. Although the focus is on respiratory care of ALS, many concepts are applicable to home respiratory care of any neuromuscular disease or restrictive thoracic disorder.

2 ∣. HISTORY OF RESPIRATORY CARE IN ALS

Initial accounts of ALS as a unique neurological pathology are credited to Jean-Marie Charcot, who discovered ALS serendipitously in the 1870s while searching for an anatomical explanation for hysteria.⁷ Respiratory complications of ALS first appeared in the literature by the mid-20th century.⁸ Concurrently, the polio epidemics gave rise to piston-driven positive pressure ventilators, rocking beds, and cuirass shell ventilators as options for providing home mechanical ventilation.⁹

One of the earliest reports of home ventilation for ALS in the 1970s describes an ALS patient managed at home for 12 months on a Puritan Bennet MA-1 respirator.¹ Even this early account of home ventilation in ALS presciently states “the real success of artificial ventilation at home is quite dependent on proper patient selection and the institution of a thorough home care program.” The article describes a family physician making house calls every 2 weeks while a respiratory therapist (RT) visited twice a week.

The emphasis on respiratory therapist involvement has been a consistent principle in multidisciplinary care for ALS. Multidisciplinary home ventilation teams for ALS first appear in the literature in 1983.^10,11 Both studies describe the RT, rather than a pulmonologist, as taking a central role for the home respiratory management. Sivak et al described the respiratory therapist assuming a leadership role on educating the patient and family on ventilator management, including cleaning, troubleshooting, and day-to-day operations. Janiszewski et al described an outpatient multidisciplinary ALS clinic at Mt. Sinai that commenced in 1978 and saw 300 ALS patients over 3 years.¹¹ Under their model, pulmonary care guidance only appeared in the latest stages of disease (stage 4), when the patient is bedridden and completely dependent for activities of daily living. Given the late stage of disease, they described the dilemma faced when “use of artificial respiratory assistance becomes the decision of the patient. The continuing decline of the patient's quality of life and its artificial prolongation often give rise to difficult ethical problems.”

The advent of NIV as a home-based therapy flourished in the 1990s. This decade marked the earliest accounts describing the benefits of NIV in motor neuron disease.^12-14 In 1997 and 1999, observational data began suggesting a significant survival improvement with use of NIV compared with refusal or minimal use.^15,16

Descriptive accounts of ALS respiratory care at the time highlight wide variability between centers of excellence in standards for pulmonary care. Melo and colleagues surveyed 20 ALS centers throughout the United States with a combined patient panel of 2,537 patients.¹⁷ Of these, 15% (n = 360) of patients were on NIV and 2.8% (n = 66) used a tracheostomy. This article emphasizes the inconsistency of pulmonologist involvement. Only 25% (5 of 20) of centers routinely involved a pulmonologist. Most (13 of 20) consulted a pulmonologist “only as needed,” whereas 10% (2 of 20) never consulted a pulmonologist.

The article's final sentence captures the authors' foresight for improving ALS respiratory care: “the variability in the current approach in monitoring pulmonary function and the modest effect of current medications to slow disease progression underscores the need to prospectively [sic] evaluate the role of NIV.” Several years later, a landmark randomized controlled trial of 41 patients with ALS suggested a significant benefit for survival and quality of life with NIV, adding fuel for a technological boom in home respiratory care over the past decade.²

3 ∣. TECHNOLOGY

3.1 ∣. Assistive ventilation devices

In the United States, the Centers for Medicare and Medicaid Services (CMS) recognizes three categories of home devices for NIV and has specific documentation requirements for each (Table 1). The first category is a respiratory assist device (RAD) and is designated by the Healthcare Common Procedure Coding System (HCPCS) codes E0470 and E0471, which indicate whether the device does not or does have a back-up respiratory rate, respectively. RADs are often referred to as “BiPAP” (a proprietary name coined originally by Philips Respironics). In general, they provide simple bilevel pressure settings, one setting preset option, an absence (or minimal presence) of alarms, and built-in humidification. They must be plugged into an external power source, thereby hindering portability. Insurance companies cover a RAD on a “lease-to-buy” model whereby an adherent patient owns the device after 13 months.¹⁸

TABLE 1.

Centers for Medicare and Medicaid Services qualifying documentation for respiratory assist devices (E0470, E0471) and portable ventilators (E0465, E0466, E0467)

Correct diagnosis	Diagnosis of neuromuscular disease or other restrictive thoracic disorder
	Test	Qualifying value	Notes	Limitations
Qualifying test	Spirometry	FVC <50% predicted
	Maximal inspiratory pressure	MIP less negative than −60 cmH2O		Poor accuracy in bulbar weakness
	Nocturnal pulse oximetry	SpO2 ≤88% for ≥5 min on nocturnal pulse oximetry	Minimum recording time 2 hours while breathing the prescribed FiO2	Low sensitivity to hypercapnia
	Arterial blood gas	PaCO2 ≥45 mmHg	Sampled while the patient is awake breathing the prescribed FiO2	Impractical for routine outpatient use
Clarifying documentation	Specific to respiratory assist devices (E0470, E0471): Documentation that chronic obstructive pulmonary disease does not significantly contribute to patient's respiratory impairment.		Specific to ventilators (E0465, E0466, E0467): Diagnosis of chronic respiratory failure Prescribing a mode and/or feature unique to ventilators (eg, mouthpiece ventilation, etc) For E0467: Ventilator qualifying criteria plus description of need for a multifunctional device

Abbreviations: FiO₂, fraction of inspired oxygen concentration; FVC, forced vital capacity; MIP, maximum inspiratory pressure; PaCO₂, arterial partial pressure of carbon dioxide; SpO₂, percent saturation of arterial blood measured by pulse oximetry.

The second category is the mechanical ventilator, which is meant to provide life support to anyone with neuromuscular disease documented as having “chronic respiratory failure” and who cannot be successfully managed on a RAD. Ventilators can be used via tracheostomy or noninvasively (HCPCS codes E0465 and E0466, respectfully). Ventilators are distinguished from RADs by offering a wider variety of settings, mouthpiece ventilation (also known as “sip ventilation”), multiple preset options (eg, one preset for night and another for day), audible alarms, and internal batteries to facilitate portability. Ventilators are significantly more expensive than RADs. CMS categorizes ventilators as requiring “frequent and substantial servicing” to avoid patient harm.¹⁸ Durable medical equipment (DME) companies receive a monthly rental payment to cover all maintenance, supplies, and home visits for the duration of device necessity.

The third category is a multifunctional device home ventilator (HCPCS code E0467). In addition to ventilation, these machines can provide supplemental oxygen, cough assistance, suction, and nebulizer delivery in one portable device. The qualifying criteria for a multifunctional device include those for mechanical ventilators plus a justification for the need for at least two of the five functions.

3.2 ∣. Airway clearance

In addition to impaired ventilation, neuromuscular respiratory weakness can also contribute to a weakened cough. A strong cough requires a well-coordinated contraction pattern of the muscles of inspiration, glottic closure, and exhalation.¹⁹ Weakened airway clearance may increase the risks for atelectasis, pneumonia, impaired gas exchange, and mucus plugging.

One can measure cough strength, also known as “peak cough flow” (PCF), using a peak flow meter or a spirometer. Multiplying by 60 will convert a spirometry peak expiratory flow (PEF) in liters/second to PCF in liters/minute. Normal values of PCF are often quoted as greater than 270 L/min for normal airway clearance; less than 160 L/min has been associated with low likelihood of tolerating extubation and may require a tracheostomy.^20,21

There are several mechanisms for improving airway clearance in ALS even at earlier stages of disease when forced vital capacity (FVC) and PCF are mildly reduced.^22,23 These techniques are most successful with intact glottic control. Glossopharyngeal breathing (“frog breathing”) and lung volume recruitment (LVR) offer low-cost techniques for sequential inhalations to augment intrathoracic pressure (“breath stacking”) before exhaling. Patients may perform LVR using a manual resuscitation bag connected to corrugated tubing, one-way valve, and anesthesia mask or mouthpiece.²⁴ Patients can learn to breath stack on a home ventilator when in volume control modes.

In the absence of specialized equipment, a trained caregiver can augment a patient's airway clearance by providing a manual assisted cough maneuver.²⁵ A manual assisted cough involves an assistant standing in front of the patient while applying firm abdominal pressure during exhalation.

In the United States, individuals with ALS can qualify for a mechanical insufflation-exsufflation (MI-E) device, also known as a cough assist device, for meeting both criteria of: (1) diagnosis of motor neuron disease or ALS; and (2) that the condition is causing a significant impairment of the chest wall and/or diaphragm, resulting in an inability to clear retained secretions.²⁶ Appearing similar to a ventilator, MI-E consists of a bedside device connected to circuit tubing and a patient interface (usually an anesthesia mask). MI-E can simulate a cough in a triphasic maneuver: (1) high-pressure insufflation; followed by (2) high negative pressure exsufflation phase and then (3) pause between the exsufflation and insufflation.

MI-E offers a variety of pressure and timing settings that must be individually customized to the patient. As an example, ALS patients with significant upper motor neuron bulbar spasticity may experience paradoxical adduction of the laryngeal muscles and vocal cords during rapid insufflation or exsufflation.²⁷ Under this scenario, settings can be tailored to ameliorate this effect while still providing adequate airway clearance.²⁸ Some MI-E devices offer an optional airway oscillation, which has yet to be proven beneficial in ALS.²⁹

3.3 ∣. Monitoring of assisted ventilation

Both RADs and portable ventilators have an internal memory that records hourly use and performance data. Many devices available in the United States today offer the ability to transmit this data wire-lessly to central web servers. Data transmit asynchronously on a daily basis, allowing clinicians remote access to a recent summary of various parameters, such as tidal volume, minute ventilation, mask leak, usage patterns, etc (Figure 1). Telemonitoring can help streamline clinician troubleshooting, particularly between office visits. Earlier work has provided a detailed review of telemonitoring for home ventilation.³⁰

FIGURE 1.

Remote ventilator data download for a patient with ALS showing total mask leak for a 24-hour period. The sawtooth pattern indicates the jaw falling away from the mask and making intermittent contact throughout the night. Addressing mask leak often takes precedence over adjusting ventilator settings.

Telemonitoring respiratory status goes beyond noninvasive ventilation machines. Several pioneers in the ALS clinical research community have described the value of remote respiratory function monitoring for a population with limited mobility.^31-33 Handheld spirometers have enabled reliable, frequent remote monitoring of respiratory function between routine clinic visits.³⁴ Many portable spirometers available today generate reports for wireless transmission to a smartphone app or directly to a clinician.

As progressive respiratory muscle weakness leads to hypoventilation and atelectasis, monitoring gas exchange via blood oxygenation and ventilation becomes essential. Although the “gold standard” is the arterial blood gas (ABG), it is impractical for routine outpatient monitoring.

Measuring oxygen saturation by pulse oximetry (SpO₂) is widely available and practical for assessing oxygenation status in a clinic or the home. Use of nocturnal SpO₂ offers utility for early NIV qualification compared with FVC.³⁵ However, any desaturation in an individual with ALS with normal lung parenchyma, airways, and vasculature is most likely related to hypoventilation causing carbon dioxide retention.

Noninvasive options for estimating arterial carbon dioxide (PaCO₂) include venous blood gas, end-tidal CO₂ (ETCO₂), and transcutaneous monitoring. Peripheral venous blood gases require a blood gas analyzer and measurements have a poor degree of correlation with PaCO₂ with wide 95% confidence intervals as large as 25 mmHg.³⁶ ETCO₂ monitoring is practical and useful for monitoring carbon dioxide trends in absence of advanced lung disease.³⁶ However, ETCO₂ measurements via nasal cannula are not feasible for simultaneous use with a noninvasive mask interface.

Transcutaneous carbon dioxide monitoring (TCO₂) is the most accurate noninvasive method for estimating PaCO₂ and has demonstrated utility for recognizing hypercapnia in ALS.^37-39 Across multiple studies, bias is minimal (less than or equal to 1 mmHg) and 95% limits of agreement are within 6 mmHg with correct sensor placement.^36,40 TCO₂ monitoring can estimate PaCO₂ in several settings: (1) spot checks in clinic; (2) concurrently with respiratory device use for simultaneous feedback during settings titration; or (3) overnight recordings (Figure 2). Some home ventilators have now incorporated TCO₂ as an additional parameter in telemonitoring reports when the machine is used simultaneously with a TCO₂ monitor. Limitations of TCO₂ include a strict maintenance schedule for optimal performance and high cost of both the device and its consumables.

FIGURE 2.

Overnight transcutaneous tracing for a patient with ALS with severe bulbar weakness and a forced vital capacity of 17% predicted. A, Original carbon dioxide (CO₂) tracing (upper line) with a drift-corrected tracing (lower line). Average CO₂ was 43.8 mmHg and time at >50 mmHg was 0 seconds. B, Simultaneous pulse oximetry tracing. The mean oxygen saturation was 95% and time at <88% was 0 seconds. The absence of hypercapnia and hypoxemia in this study allowed the patient to defer noninvasive ventilation until a later date.

4 ∣. CURRENT STATE OF RESPIRATORY CARE IN ALS

4.1 ∣. Provision of respiratory care in ALS clinics

In the United States, the foundational guidelines for respiratory care in ALS arise from the American Academy of Neurology (AAN) recommendations on respiratory and multidisciplinary care.^41,42 Both the AAN guidelines and CMS use criteria for initiating NIV based on an expert consensus statement published in 1999.⁴³ Consequently, most ALS clinics focus their respiratory monitoring around measuring FVC, maximum inspiratory pressure (MIP), and nocturnal pulse oximetry.

Guidelines and organizations vary on recommendations for involving a pulmonologist in ALS care. The AAN guidelines do not mention involving a pulmonologist, and instead suggest involving a respiratory therapist as part of a multidisciplinary team.⁴¹ National organizations such as the ALS Association (ALSA) and Muscular Dystrophy Association (MDA) offer financial incentives to form multidisciplinary outpatient clinics.^44,45

ALSA recommends that pulmonologists focus on advising “…people living with ALS regarding major decisions about long-term respiratory and nutritional support.”^44,45 Although the overarching message from ALSA seems to suggest that a respiratory therapist drives respiratory care under most circumstances, ALSA recommendations do acknowledge that a pulmonologist may work collaboratively with the respiratory therapist.⁴⁴ In contrast with ALSA and AAN guidelines, the MDA clearly designates (and requires) an MDA/ALS Care Center to include a pulmonologist as a core part of the team.⁴⁵

As an update to the 1999 Melo et al article mentioned previously, one of the most compelling recent reviews of practice patterns of respiratory care in ALS was published in 2018 by Heiman-Patterson et al.⁴⁶ In a 2016 survey of centers within the Northeast ALS (NEALS) consortium on NIV practice patterns, 68% (39 of 57) of US respondents reported that initial NIV set-up was routinely performed in the patient's home by a respiratory therapist. Just over half of US centers reported early pulmonologist involvement, as 18 of 57 (32%) had the patient seen by a pulmonologist the same day, whereas 15 of 57 (26%) referred to a pulmonologist/other specialist outside of the ALS clinic for initiation of NIV. A low percentage of US centers (11 of 57, 19%) reported that a pulmonologist decides what type of equipment to use, significantly fewer than the 25 of 39 (64%) European respondents.

4.2 ∣. Initiation and monitoring of respiratory support

Inconsistent pulmonary engagement has caused many ALS clinics to develop processes for prescribing NIV in the absence of an engaged pulmonologist. Anecdotally, and as indicated earlier, NIV for patients seen at ALS centers in the US often is initiated when a neurologist submits a prescription to a DME company for in-home set-up by a respiratory therapist. Initial device settings may unintentionally cause discomfort and interrupt sleep. Thereafter, several successive, frequent iterations during outpatient visits may be necessary to attain NIV settings which both: (a) provide restorative sleep, and (b) normalize nocturnal gas exchange.

An elective inpatient admission for NIV settings titration would suffice to avoid some of the pitfalls of the initiation process; however, current US payor guidelines necessitate a qualifying acute decompensation diagnosis for hospital admission.³⁷ Unfortunately, some patients are initiated on nocturnal NIV only after acute respiratory failure leads to intensive care unit (ICU) admission. If the patient is fortunate enough to survive without a tracheostomy, then NIV is prescribed upon hospital discharge. In Europe, ALS patients starting NIV commonly undergo a 3- to 7-day inpatient admission for nocturnal settings titration.⁵ One US study suggested that elective inpatient NIV initiation may be effective for ALS patients with chronic hypercapnia.³⁷

4.3 ∣. Gaps in care

Technological advancements over the last two decades have produced several proprietary devices, software, and treatment algorithms that have created a new pulmonary niche focused on the outpatient management of chronic respiratory failure. Meanwhile, specialist training has struggled to maintain pace with the latest home respiratory care capabilities. With the birth of a new specialty combined with a dearth of master clinicians, several critical gaps have surfaced in the home respiratory care of ALS.

4.3.1 ∣. Identifying optimal thresholds for initiating noninvasive ventilation

Although evidence suggests that NIV likely improves survival in ALS,^2,47,48 the ideal time for NIV initiation remains unclear. Current CMS documentation requirements heavily influence practice patterns for qualifying someone with ALS for a RAD or a ventilator (Table 1). Neurologists have employed vital capacity, either slow (SVC) or forced (FVC), as a surrogate of respiratory muscle strength in ALS. FVC has been shown to correlate with survival in ALS.^49-54 FVC trajectories may suggest distinct respiratory phenotypes.⁵⁵ Spirometry maneuvers are convenient, relatively inexpensive, and have demonstrated reliability across a wide variety of outpatient settings.^56,57

However, the FVC is not without significant limitations. Current guidelines and payor criteria for NIV qualification require an FVC of less than 50% predicted normal---a threshold that has not been rigorously studied and originally chosen based on observational data that are now almost 50 years old.^43,58 Evidence has demonstrated improved survival with NIV initiation at higher FVC, suggesting that nocturnal hypoventilation may occur well before the 50% threshold.⁵⁹ Experienced ALS clinicians are aware of the FVC difficulties in the setting of significant bulbar weakness. Finally, there is international discrepancy on the FVC thresholds for NIV initiation, as European guidelines suggest starting NIV once FVC is under 80% predicted in the presence of respiratory symptoms.³ A United States technical expert panel recently proposed new criteria for NIV qualification in neuromuscular disease (Table 2).⁶⁰ Notable changes include accepting a vital capacity of less than 80% in the presence of symptoms, and use of noninvasive carbon dioxide measurements (ie, end-tidal and transcutaneous) to document hypercapnia. As of this writing, a response from the CMS is pending.

TABLE 2.

ONMAP technical expert panel recommended criteria for initiating noninvasive ventilation for neuromuscular disease and other thoracic restrictive disorders

Any one of the following criteria are required:
Measurement	Notes
Vital capacity <80% predicted with symptoms	Dyspnea, morning headache, orthopnea, daytime sleepiness, or unrefreshing sleep
Vital capacity ≤50% predicted with or without symptoms	Forced vital capacity or slow vital capacity
Hypercapnia	Daytime awake PaCO2 ≥45 mmHg via ABG or End-tidal, transcutaneous, or venous CO2 ≥50 mmHg
Oxygen desaturation during polysomnography or home sleep test	SpO2 ≤90% for ≥5% of the night or SpO2 ≤88% for ≥5 minutes
Maximum inspiratory pressure	Equal to or worse than −60 cmH2O
Sniff nasal inspiratory pressure	Equal to or worse than −40 cmH2O

Note: Reproduced with permission from Elsevier (DOI: https://doi.org/10.1016/j.chest.2021.05.075). Adapted from Wolfe et al.⁶⁰

Abbreviations: ABG, arterial blood gas; CO₂, carbon dioxide; ONMAP, Optimal Noninvasive Medicare Access Promotion; PaCO₂, arterial partial pressure of carbon dioxide; SpO₂, oxygen saturation measured by pulse oximetry.

Beyond FVC, clinicians should be aware of the alternative measurements of respiratory muscle strength. MIP offers an alternative static measurement subject to inaccuracy with bulbar weakness. Sniff nasal inspiratory pressure using nasal plugs can bypass bulbar limitations, but it requires specific equipment and can be falsely low in the presence of nasal congestion.⁶¹ Other measurements of static respiratory strength, such as transdiaphragmatic inspiratory pressure, are invasive and require specialized expertise for accurate performance.⁶²

Clinicians suspicious of early hypoventilation may request an overnight pulse oximetry to qualify for NIV. Unfortunately, current evidence suggests that nocturnal pulse oximetry has only 70% sensitivity for detecting nocturnal hypercapnia.^63-65

Putting all this together, the standard measurements of respiratory insufficiency are limited by potentially delayed recognition with daytime static measurements and low sensitivity with nocturnal pulse oximetry. The arterial blood gas is the gold standard for assessing hypoventilation; however, it is invasive, represents a snapshot in time, and remains impractical for outpatient use.

4.3.2 ∣. Rate of NIV acceptance

Despite the potential benefits of NIV, the literature suggests a significant gap exists in optimal NIV uptake. A 10-year observational study showed that approximately 40% of ALS patients never received a prescription for NIV.⁴⁷ Data from the Pooled Resource Open-Access Clinical Trials Database (PRO-ACT) indicate that 48% of ALS patients started NIV later than guideline recommendations.⁶⁶ Among subjects initiated on NIV, approximately 15% (88 of 604) subsequently discontinued NIV, and 82% of discontinuations occurred within the first 6 months.⁶⁶ The reasons for NIV intolerance may be multifactorial and warrant further study.

4.3.3 ∣. Financial barriers

Costs will vary by stage of disease, but one study showed that the annual per-patient health system costs of ALS is approximately $63, 693.⁶⁷ Most of this is distributed among DME companies for servicing wheelchairs and ventilators. Outpatient care of neuromuscular disease involves relatively low-revenue-generating services compared with conditions that commonly require procedural interventions. The financial strain on the health-care system is further compounded by the extreme time commitment required for prolonged office visits and the high burden of care coordination between appointments.

Combining low reimbursement with prolonged care times creates a lack of financial incentive for pulmonary divisions and health systems to develop centers of excellence in the respiratory care of neuromuscular disease. Although billing codes exist for prolonged care time, they are applicable only under strict circumstances.⁶⁸ Respiratory therapists cannot bill for their services, minimizing additional revenue for outpatient clinics and DME companies. As described previously under the section “Assistive ventilation devices,” DME companies receive minimal payments after 13 months for RADs and a fixed monthly bundled payment for home ventilators. There are no additional financial incentives for RT services beyond ensuring the patient is using the device for over 4 hours/day, on average.¹⁸ Even under the ventilator model with a fixed monthly payment as a numerator, DMEs are under heavy pressure to control the denominator (ie, home visits and supplies) to improve financial revenue. Patients covered by Medicare alone (without a secondary insurance) are responsible for covering 20% of out-of-pocket costs, which may amount to ~$200/month for a ventilator.⁶⁹

A shift from RADs to increased use of home ventilators in the United States has greatly increased costs for insurance systems.⁷⁰ Consequently, some private insurance companies have begun denying ventilator coverage for ALS until the patient demonstrates physiological failure of an RAD. Initially starting with a RAD may be appropriate for slowly progressing disease while having the added benefits of lower cost and eventual ownership of a back-up device to a ventilator. As the disease progresses, the RAD may be insufficient and a ventilator should be considered for various reasons. For example, as daytime support becomes necessary, RADs may hinder mobility (and thus quality of life) while restricting ventilation options.

4.3.4 ∣. Variability of pulmonologist involvement

Although RTs are invaluable to the overall care of patients on home NIV, unfortunately they are not licensed to perform many of the critical responsibilities that comprise ALS respiratory care such as: signing off on treatment plans; writing orders for medical devices; prescribing medications; or performing preoperative risk assessments. Altering a treatment plan in the context of deranged renal, cardiac, or volume status physiology may require multidisciplinary assessment beyond the scope of a respiratory therapist alone.

Despite the ALSA and MDA providing financial support for clinics to incorporate a pulmonologist, there is a meager pipeline of rising physician trainees seeking specialization in home ventilation respiratory care. The etiology of this void is likely multifactorial. Although home respiratory care of ALS has been described since the 1970s,⁷¹ the recent evolution of technological devices makes this a relatively “young” specialty. With few mid- and late-career pulmonologists dedicated to this medical niche, there is a scarcity of mentors grooming protégés on this career path.

4.3.5 ∣. Paucity of active research

There is a deficiency of active clinical research in the respiratory dysfunction of ALS. A search for “amyotrophic lateral sclerosis respiratory care” on NIH RePORTER as of this writing yields 19 active research studies.⁷² Of these, four investigated respiratory dysfunction specifically in ALS, including one basic science study and three observational studies. During the preparation of this article, the NIH released a notice of special interest for grants focusing on the respiratory complications of muscular dystrophies.⁷³ The National Institute of Neurological Disorders and Stroke recently drafted a strategic plan of research initiatives for ALS, which prioritizes “optimizing the quality of life of people living with ALS and their caregivers.”⁷⁴ The NIH clearly supports research in the respiratory care of neuromuscular disease; however, a meager amount of actively funded studies may suggest scarce application submissions.

Outside of federal support, foundational support exists but offers boundaries for early-career pulmonary physician scientists performing clinical research in ALS. As an example, collaborative funding announcements through the ALSA and AAN for early-career investigators require that award recipients be an AAN member and have completed residency no more than 7 years before start of the award, even if the fellowship was completed.⁷⁵ In the United States, a neuromuscular disorders fellowship most frequently lasts 1 year, whereas a pulmonary and critical care fellowship often spans 3 to 4 years. Similar limitations exist for the MDA Development Grant, which stipulates that applicants must be no more than 9 years from receipt of their medical degree.⁷⁶ As a comparison, the American Thoracic Society funding opportunities define the early-stage investigator eligibility window as within 12 years from a terminal degree.⁷⁷

4.3.6 ∣. Lack of formal education

The Accreditation Council for Graduate Medical Education stipulates that pulmonary and critical care fellows demonstrate competence in the management of outpatients with chronic respiratory failure with neuromuscular disorders.⁷⁸ However, most fellowship exposure to this topic includes acute respiratory failure in the ICU. ALS patients admitted to an ICU are at high risk of undergoing tracheostomy before being transferred to a long-term care facility, which is typically devoid of pulmonary trainees. In the outpatient setting, few centers around the country have designated home ventilation clinics that concentrate patients among a handful of invested experts. Among those few centers, a fraction include a pulmonologist in their ALS clinic.⁴⁶

Guidelines on the respiratory care of ALS focus heavily on thresholds for initiating noninvasive ventilation.⁴² Few studies have addressed the subsequent (and meticulous) steps involved in tailoring the NIV devices and their myriad of settings to deliver effective, comfortable ventilation. Most of the evidence guiding best practices is based on expert opinion, with few clinical trials in the pipeline.

The absence of a formal educational curriculum, fellowship program, or guidelines has created a critical knowledge gap among pulmonologists for managing respiratory complications of neuromuscular disease. Neurologists have recognized this gap. In being dedicated to their patients, neurologists have learned to identify and address early respiratory insufficiency in ALS. Depending on local center expertise, neurologists may hesitate to refer to pulmonologists until advanced respiratory failure, when NIV seems intolerable and tracheostomy appears imminent.

4.3.7 ∣. Tailoring noninvasive ventilation vs tracheostomy

Despite recent technological advancements in respiratory care delivery, the concept of “optimal” respiratory care for ALS patients remains undefined. The latest AAN ALS respiratory care guidelines (2009) were published well before the widespread use of auto-adjusting home ventilators, transcutaneous carbon dioxide monitoring, and ventilator data telemonitoring. Neither the American Thoracic Society nor the American College of Chest Physicians has published guidelines on optimizing the management of long-term hypoventilation in ALS.

With few physicians practicing in this area of pulmonary medicine, and even fewer trainees in the pipeline, a scarcity of active clinical research, and an absence of guidelines on optimizing respiratory therapy, ALS patients are left to receive highly variable care subject to their local center practice patterns. Home DME respiratory therapists and office clinicians with limited or no formal training in home ventilation may prescribe home ventilators in auto-adjusting modes with generic settings and wide parameter ranges. For a large proportion of patients, this “one-size-fits-all” therapy may lead to premature NIV intolerance.

Often NIV discomfort may be viewed as a device failure; however, the more likely scenario is that settings have not been modified to keep up with patients’ evolving muscle weakness, chest wall compliance, and secondary lung impairment in ventilation and gas exchange. Barring recurrent aspiration or severe upper airway dysfunction, ALS patients receiving attentive expert care can successfully use noninvasive ventilation up to 24 hours/day. Such a goal may be incredibly difficult to achieve, or unwanted by the patient, but reaching this goal is possible at a center with a dedicated team willing to make iterative adjustments and frequently review telemonitoring data.

Therein lies a dilemma.

Akin to the “ethical problems” first described in 1983 by Janiszweski et al,¹¹ optimized ventilation and comfort at every disease stage will push patients deeper into advanced ALS as extrarespiratory motor function deteriorates. People with ALS and their caregivers may endure prolonged consequences of functional loss, progressing symptoms, and late-stage complications, which has created controversy over whether chronic NIV in ALS provides meaningful therapy.⁷⁹

Conversations about tracheostomy often include descriptions of the locked-in state and caregiver burden, which may act as deterrents to prolonging a devastating disease. At the point of respiratory discomfort on NIV, offering tracheostomy vs hospice has traditionally created a standardized pivot point, providing the individuals with autonomy on whether to endure advancing disease. For better or for worse, expert NIV care delays this pivot point further into more advanced stages of ALS. Additional complications may arise, such as communication barriers, intolerable secretions, or malnutrition from deferring gastrostomy tube placement due to the expectation of death from respiratory failure before developing severe malnourishment.

5 ∣. BRINGING RESPIRATORY CARE FOR ALS UP TO SPEED

Although several critical gaps exist in the respiratory care of ALS, steadfast efforts from a variety of perspectives may offer some viable solutions (Table 3).

TABLE 3.

Current gaps and proposed solutions for ALS respiratory care

Current gap	Potential solutions
Lack of formal education	Online education resources Home ventilation/chronic NIV fellowship
Paucity of active research	Increase grant submission rate Extend neurology organization eligibility windows for young investigator funding Create home ventilation registry
Financial barriers	Leverage available CPT codes for prolonged care Lobby for respiratory therapist billing privileges Financial support for multidisciplinary care
Variability in pulmonologist involvement	Foundational support Insurance incentives Health system service line support Philanthropy
Rate of NIV acceptance	Elevate standard of respiratory care to include a quantitative, iterative approach to managing NIV

Abbreviations: ALS, amyotrophic lateral sclerosis; CPT, Current Procedural Terminology; NIV, noninvasive ventilation.

5.1 ∣. Professional education

The breadth of the education gap for ALS home ventilation care is unclear, but sold-out home ventilation workshops at annual academic pulmonary conferences are hard evidence of the existing educational void. Until completion of such a rigorous training needs assessment,⁸⁰ there are approaches that may lead to improved educational opportunities.

Online educational webinars taught by content experts in ALS respiratory care

This approach may include a series of brief videos (20 to 30 minutes) covering a spectrum of topics (and subtopics) with a focus on ALS-specific needs such as assisted ventilation devices and strategies, initiation of home-assisted ventilation, airway clearance, troubleshooting, and palliative and end-of-life care, among others. Most importantly, this webinar series must be widely available for equitable distribution. The target audience would include any clinician interested in learning how to improve respiratory care for their ALS patients. The ALS Finding a Cure Foundation and philanthropic support has funded such a course and it is currently in production as of this writing.

Home-assisted ventilation/chronic noninvasive ventilation fellowship

This approach could be a 1-year advanced fellowship for senior pulmonary and critical care fellows and jointly directed by specialists in pulmonary and sleep medicine. Fellows would spend 1 year experiencing both in- and outpatient clinical rotations, navigating hospital-to-home transitions, focusing on home ventilation technology, and conducting pertinent clinical research. As an added incentive, graduating fellows would be board-eligible in sleep medicine. Such an initiative would require several core ingredients, including buy-in support from a center of excellence; curriculum development through sleep medicine, pulmonology, and neurology; and a funding source for salary, benefits, and equipment. A successful program would produce a pipeline of trainees focused on home ventilation expertise capable of establishing centers of excellence around the country. Such a fellowship may blend well with the Sleep Medicine Advancing Innovation in Residency Education (AIRE) pilot program, which allows for sleep medicine education during additional specialty training, such as pulmonary and critical care fellowship.⁸¹

5.2 ∣. Clinical research

Given the scarcity of actively funded federal projects on respiratory care in ALS, a natural solution would include increasing the submission rate via creating trainee opportunities. Concurrently, nonfederal neurology-focused organizations (eg, ALSA and MDA) extending early-career eligibility windows for pulmonologists may open opportunities for investigating respiratory insufficiency in ALS.

Several strategies may facilitate increased grant submissions and funding. A focus on early career trainees, such as an NIV fellowship, would provide structure and protected space for cultivating research ideas. We also need more respiratory-focused data. Currently active ALS clinical trials record basic respiratory measurements (eg, vital capacity, use of NIV, and patient-reported daily hourly usage), which creates potential for collaborative efforts if trial sponsors share access to the respiratory data.

Another avenue for respiratory data includes remote ventilator telemonitoring. Home ventilator manufacturers have created propriety online web servers which upload ventilator usage and performance data daily. Although these were originally designed for use by clinicians to analyze on a patient-by-patient basis, the abundance of data storage creates the potential for analyses at the cohort level. Combining bedside clinical and demographic data with online telemonitoring data may lead to the first home ventilation patient registry. Interested clinicians could begin using these longitudinal data to look at geographic practice patterns, analyze outcomes by therapy strategy, or begin to design multicenter interventional clinical trials aimed at improving clinical outcomes. Once funding is available, such a registry would be relatively “low-hanging fruit” to feed clinical research.

5.3 ∣. Financial initiatives

As mentioned previously, the care of ALS patients has several components that hinder financial revenue such as prolonged office visits, significant care coordination time between office visits, and few avenues for revenue-generating services (such as procedures and inpatient visits). Several Current Procedural Terminology (CPT) codes allow billing for prolonged care. Examples include CPT codes for prolonged face-to-face care (G2212), non–face-to-face care coordination time (99358/9), and for reviewing remote physiologic data (99457/8, 99091).⁶⁸ Clinicians should carefully note that these CPT codes apply under specific circumstances once a clinician spends a minimum time commitment (eg, more than 30 minutes) on a single calendar day. The reader is referred to previous work for further details on CPT codes.^30,68

Beyond CPT codes, lobbying for billable services for respiratory therapists may make the delivery of home ventilation services more financially viable. The various educational pathways for becoming a registered respiratory therapist have partially hindered efforts for direct billing privileges. Successful advocacy for CPT codes 99453, 99454, and 99457 now offers the ability to bill for remote physiological monitoring, providing an indirect path for reimbursing respiratory therapist time. The Creating Opportunities Now for Necessary and Effective Care Technologies (CONNECT) for Health Act of 2021 advocates for inclusion of respiratory therapists in telehealth medicine and aims to expand coverage of telehealth services under Medicare.⁸² Under the guidance of a physician's care plan, respiratory therapists may offer additional encounters to spend the necessary time for education, optimizing interfaces and settings, and ensuring adequate ventilation. Additional financial support for a multidisciplinary approach to ALS care would incentivize health systems to involve pulmonary physicians. Beyond the current support from the ALSA and MDA, financial incentives may come from multiple sources, such as: (a) insurance companies for meeting specific metrics; (b) from within existing health system service lines; or (c) externally via philanthropic efforts. A comprehensive, multidisciplinary approach to ALS respiratory care may minimize hospitalizations for acute respiratory failure, reduce need for emergent tracheostomy, improve patient-reported outcome measures, and facilitate developing clinical research initiatives.

5.4 ∣. A new standard of care

Office visits present opportunities for the clinician to assess NIV tolerance in real time during a ventilator titration session. The patient and caregiver should ideally bring their home equipment into the clinic. During a prolonged visit, a physician and respiratory therapist work together to assess mask fit, device function, and patient comfort with proposed settings.

A typical in-office ventilator titration session is illustrated in Figure 3. The respiratory therapist can attend to hands-on demonstrations of mask donning and adjusting ventilator settings. If available, concurrent use of a transcutaneous carbon dioxide monitor can provide real-time physiological response to setting adjustments. The physician (not shown in Figure 3) can review recent telemonitoring data, guide the patient and caregiver through the process, and document significant findings. A well-trained clinician can leverage the various device options to ensure patient comfort throughout every phase of the breath, as shown in Figure 4. As ALS progresses, volitional inspiratory effort will wane as the chest wall compliance decreases. Consequently, patients' respiratory support needs will evolve along with optimal device settings, further necessitating office visits for necessary adjustments. As described previously in the “Financial initiatives” subsection, CPT codes for prolonged care may capture the added time necessary for these time-consuming visits.

FIGURE 3.

In-office ventilator titration session. Man with ALS on a ventilator (background) with a transcutaneous carbon dioxide (CO₂) monitor (right) providing simultaneous CO₂ via sensor attached to the right earlobe. The respiratory therapist (left) attends to mask fitting and ventilator settings adjustment. The physician (not shown) focuses on patient communication and documentation.

FIGURE 4.

Pressure-time curve of the breath cycle under positive pressure ventilation. Respiratory device settings can be tailored to address each of the phases shown. EPAP, expiratory positive airway pressure; IPAP, inspiratory positive airway pressure.

Finally, leveraging respiratory device telemonitoring for all patients will provide an additional level of clarity for optimizing settings. Such data can be critical for troubleshooting between office visits or during setting titration sessions as described above.

6 ∣. CONCLUSION

Home ventilation for ALS has progressed considerably in the last 50 years. Multidisciplinary programs, compact home ventilators, and telemonitoring allow a sophisticated approach to respiratory care. Unfortunately, we still have a long way to go until physician education facilitates mastery of this rapidly evolving technology. Even the most dedicated neurologists cannot do this alone---qualified pulmonary and sleep medicine physicians must answer the call. We need a multifaceted approach for closing the critical gaps in current ALS respiratory care. Short of a cure for ALS, respiratory care will continue to remain a core focus of a multidisciplinary plan to prolong survival and improve quality of life. Through teamwork, compassion, and focused initiatives we can alleviate the suffering and offer comfort for those enduring this challenging disease.

Abbreviations:

AAN

American Academy of Neurology

ABG

arterial blood gas

AIRE

Advancing Innovation in Residency Education

ALS

amyotrophic lateral sclerosis

ALSA

Amyotrophic Lateral Sclerosis Association

CMS

Centers for Medicare and Medicaid Services

CONNECT

Creating Opportunities Now for Necessary and Effective Care Technologies

CPT

Current Procedural Terminology

DME

durable medical equipment

ETCO₂

end-tidal carbon dioxide

FVC

forced vital capacity

HCPCS

Healthcare Common Procedure Coding System

ICU

intensive care unit

MDA

Muscular Dystrophy Association

MI-E

mechanical insufflation-exsufflation

MIP

maximum inspiratory pressure

NEALS

Northeast Amyotrophic Lateral Sclerosis consortium

NIV

noninvasive ventilation

PaCO₂

partial pressure of arterial carbon dioxide

PCF

peak cough flow

PEF

peak expiratory flow

PRO-ACT

Pooled Resource Open-Access Clinical Trials Database

RAD

respiratory assist device

RT

respiratory therapist

SpO₂

oxygen saturation by pulse oximetry

SVC

slow vital capacity

TCO₂

transcutaneous carbon dioxide

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no new data were created or analyzed in this study.