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

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.

Classifying Patients with Amyotrophic Lateral Sclerosis by Changes in FVC. A Group-based Trajectory Analysis.

Rationale: A model for stratifying progression of respiratory muscle weakness in amyotrophic lateral sclerosis (ALS) would identify disease mechanisms and phenotypes suitable for future investigations. This study sought to categorize progression of FVC after presentation to an outpatient ALS clinic.Objectives: To identify clinical phenotypes of ALS respiratory progression based on FVC trajectories over time.Methods: We derived a group-based trajectory model from a single-center cohort of 837 patients with ALS who presented between 2006 and 2015. We applied our model to the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database with 7,461 patients with ALS. Baseline characteristics at first visit were used as predictors of trajectory group membership. The primary outcome was trajectory of FVC over time in months.Measurements and Main Results: We found three trajectories of FVC over time, termed "stable low," "rapid progressor," and "slow progressor." Compared with the slow progressors, the rapid progressors had shorter diagnosis delay, more bulbar-onset disease, and a lower ALS Functional Rating Scale-Revised (ALSFRS-R) total score at baseline. The stable low group had a shorter diagnosis delay, lower body mass index, more bulbar-onset disease, lower ALSFRS-R total score, and were more likely to have an ALSFRS-R orthopnea score lower than 4 compared with the slow progressors. We found that projected group membership predicted respiratory insufficiency in the PRO-ACT cohort (concordance statistic = 0.78, 95% CI, 0.76-0.79).Conclusions: We derived a group-based trajectory model for FVC progression in ALS, which validated against the outcome of respiratory insufficiency in an external cohort. Future studies may focus on patients predicted to be rapid progressors.

Development of a prognostic model of respiratory insufficiency or death in amyotrophic lateral sclerosis.

A clinically useful model to prognose onset of respiratory insufficiency in amyotrophic lateral sclerosis (ALS) would inform disease interventions, communication and clinical trial design. We aimed to derive and validate a clinical prognostic model for respiratory insufficiency within 6 months of presentation to an outpatient ALS clinic.We used multivariable logistic regression and internal cross-validation to derive a clinical prognostic model using a single-centre cohort of 765 ALS patients who presented between 2006 and 2015. External validation was performed using the multicentre Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database with 7083 ALS patients. Predictors included baseline characteristics at first outpatient visit. The primary outcome was respiratory insufficiency within 6 months, defined by initiation of noninvasive ventilation, forced vital capacity (FVC) <50% predicted, tracheostomy, or death.Of 765 patients in our centre, 300 (39%) had respiratory insufficiency or death within 6 months. Six baseline characteristics (diagnosis age, delay between symptom onset and diagnosis, FVC, symptom onset site, amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R) total score and ALSFRS-R dyspnoea score) were used to prognose the risk of the primary outcome. The derivation cohort c-statistic was 0.86 (95% CI 0.84-0.89) and internal cross-validation produced a c-statistic of 0.86 (95% CI 0.85-0.87). External validation of the model using the PRO-ACT cohort produced a c-statistic of 0.74 (95% CI 0.72-0.75).We derived and externally validated a clinical prognostic rule for respiratory insufficiency in ALS. Future studies should investigate interventions on equivalent high-risk patients.

Practical Guide to Management of Long-Term Noninvasive Ventilation for Adults With Chronic Neuromuscular Disease.

Recent technological advances in respiratory support and monitoring have dramatically enhanced the utility of long-term noninvasive ventilation (NIV). Improved quality of life and prolonged survival have been demonstrated for several common chronic neuromuscular diseases. Many adults with progressive neuromuscular respiratory disease can now comfortably maintain normal ventilation at home to near total respiratory muscle paralysis without needing a tracheostomy. However, current practice in many communities falls short of that potential. Mastery of the new technology calls for detailed awareness of the respiratory cycle; expert knowledge of mechanical devices, facial interfaces, and quantitative monitoring tools for home ventilation; and a willingness to stay current in a rapidly expanding body of clinical research. The depth and breadth of the expertise required to manage home assisted ventilation has given rise to a new focused medical subspecialty in chronic respiratory failure at the interface between pulmonology, critical care, and sleep medicine. For clinicians seeking pragmatic "how to" guidance, this primer presents a comprehensive, physician-directed management approach to long-term NIV of adults with chronic neuromuscular respiratory disease. Bi-level devices, portable ventilators, ventilation modalities, terminology, and monitoring strategies are reviewed in detail. Building on that knowledge base, we present a step-by-step guide to initiation, refinement, and maintenance of home NIV tailored to patient-centered goals of therapy. The quantitative approach recommended incorporates routine monitoring of home ventilation using technologies that have only recently become widely available including cloud-based device telemonitoring and noninvasive measurements of blood gases. Strategies for troubleshooting and problem solving are included.

Lowering PCO2 With Noninvasive Ventilation Is Associated With Improved Survival in Chronic Hypercapnic Respiratory Failure.

BACKGROUND: Chronic hypercapnic respiratory failure is associated with high mortality. Although previous work has demonstrated a mortality improvement with high-intensity noninvasive ventilation in COPD, it is unclear whether a PCO2 reduction strategy is associated with improved outcomes in other populations of chronic hypercapnia. METHODS: The objective of this study was to investigate the association between PCO2 reduction (by using transcutaneous PCO2 as an estimate for PaCO2 and survival in a broad population of individuals treated with noninvasive ventilation for chronic hypercapnia. We hypothesized that reductions in PCO2 would be associated with improved survival. Therefore, we performed a cohort study of all the subjects evaluated from February 2012 to January 2021 for noninvasive ventilation initiation and/or optimization due to chronic hypercapnia at a home ventilation clinic in an academic center. We used multivariable Cox proportional hazard models with time-varying coefficients and PCO2 as a time-varying covariate to test the association between PCO2 and all-cause mortality and when adjusting for known cofounders. RESULTS: The mean ± SD age of 337 subjects was 57 ± 16 years, 37% women, and 85% white. In a univariate analysis, survival probability increased with reductions in PCO2 to < 50 mm Hg after 90 d, and these remained significant after adjusting for age, sex, race, body mass index, diagnosis, Charlson comorbidity index, and baseline PCO2 . In the multivariable analysis, the subjects who had a PaCO2 < 50 mm Hg had a reduced mortality risk of 94% between 90 and 179 d (hazard ratio [HR] 0.06, 95% CI 0.01-0.50), 69% between 180 and 364 d (HR 0.31, 95% CI 0.12-0.79), and 73% for 365-730 d (HR 0.27, 95% CI 0.13-0.56). CONCLUSIONS: Reduction in PCO2 from baseline for subjects with chronic hypercapnia treated with noninvasive ventilation was associated with improved survival. Management strategies should target the greatest attainable reductions in PCO2 .

Telemonitoring for Home-assisted Ventilation: A Narrative Review.

The recent advent of remote ventilator telemonitoring has the potential to revolutionize home-assisted ventilation care in the United States and elsewhere. Home ventilation machines (i.e., respiratory assist devices and portable ventilators) can now wirelessly transmit usage and performance data to cloud-based web servers for remote access by participating clinicians. In this Focused Review, we provide an update on available technology, suggest practical applications for clinical care and research, and review supporting literature. Remote monitoring permits early data review, refinement of device settings to optimize ventilatory function, and troubleshooting if a new problem arises after initial setup. Data from home spirometry and noninvasively measured blood gas tensions can complement ventilator data to reflect physiological response. Acknowledging a paucity of published outcome studies, remote telemonitoring may be a cost-effective strategy to reduce emergency room visits, urgent clinic appointments, and hospitalizations. Ongoing clinical trials in Europe aim to expand on the benefit of this rapidly evolving technology. However, several barriers may hinder widespread implementation, especially in the United States. Clinicians must familiarize themselves with each ventilator manufacturer's proprietary software to safely leverage this technology for improving care. Legal and ethical considerations threaten clinician interest. Medical insurance payers must adapt a reimbursement scheme to incentivize clinicians and durable medical equipment companies to perform this time-consuming service. Cohort-level ventilator data will facilitate multicenter clinical trials focused on improving the respiratory care of this vulnerable population.

Noninvasive Ventilation Use Is Associated with Better Survival in Amyotrophic Lateral Sclerosis.

Rationale: Noninvasive ventilation (NIV) is standard of care in amyotrophic lateral sclerosis (ALS), yet few data exist regarding its benefits.Objectives: We sought to identify whether the use of NIV was associated with survival in ALS.Methods: This was a single-center retrospective cohort study of 452 patients with ALS seen between 2006 and 2015. We matched one or more NIV subjects (prescribed NIV) to non-NIV subjects (never prescribed NIV) without replacement. The outcome was time from NIV prescription date (NIV subjects) or matched date (non-NIV subjects) until death. We performed a multivariable Cox proportional hazards model with NIV hourly usage as a time-varying covariate and stratified by matched groups.Results: After creating 180 matched groups and adjusting for age, body mass index, ALS Functional Rating Scale Revised dyspnea score, and hourly NIV use, NIV was associated with a 26% reduction in the rate of death compared with non-NIV subjects (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.57-0.98; P = 0.04). Among those with limb-onset ALS, NIV subjects had a 37% lower rate of death compared with non-NIV subjects (HR, 0.63; 95% CI, 0.45-0.87; P = 0.006). Among NIV subjects, we found that NIV use for an average of ≥4 h/d was associated with improved survival.Conclusions: NIV use was associated with significantly better survival in ALS after matching and adjusting for confounders. Increasing duration of daily NIV use was associated with longer survival. Randomized clinical trials should be performed to identify ideal thresholds for improving survival and optimizing adherence in ALS.

Successful Implementation of an Automated Sedation Vacation Process in Intensive Care Units.

This quality improvement initiative sought to develop a sedation vacation (SV) protocol to increase SV performance and ensure sustainability. A standardized, nurse-driven SV protocol within the electronic medical record was implemented in adult intensive care units (ICUs) at Boston Medical Center. For 6 months, data were collected on the number of assessments performed, SV completion, SV eligibility, and reason for exclusion. Secondary outcomes included ICU length of stay (LOS) and ventilator LOS. Of 1730 patient-days during this 6-month period, SV assessments were performed 70% (n = 1211) of the time. SVs were conducted on 60.0% (n = 726) during days in which an assessment occurred. There was no significant change in ICU LOS or ventilator LOS during the study period. This SV protocol attained a 70% adherence rate, which was sustained over the 6-month period. There were no significant changes in secondary outcomes.

Hypertension management in a student-run free clinic: meeting national standards?

PURPOSE: Affecting one in three adults, hypertension is one of the most prevalent disorders in the United States. The purpose of this analysis was to evaluate, using national care guidelines and quality standards, the quality of care provided at the Student Family Health Care Center (SFHCC) of the University of Medicine and Dentistry of New Jersey (Newark). METHOD: The authors performed a chart review of all patients seen from June 2008 to June 2009, collecting the following data: age, gender, ethnicity, body mass index, most recent blood pressure measurement, comorbid conditions, number of visits, free medications dispensed, and smoking status. The authors used the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines and Healthy People 2010 quality standards to analyze results. RESULTS: Of the 119 SFHCC patients seen during the study period, 60 had a diagnosis of hypertension. Overall, 30 (50%) of these patients were at target blood pressure. Of the 19 patients (32% of 60) with diabetes and hypertension, 5 (26%) were controlled compared with 25 (61% of 41) with hypertension only. Thirty-eight patients (63%) were taking a thiazide, 42 (70%) were on multidrug regimens, and all 19 of the patients with diabetes (100%) were on an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, as per the JNC 7 guidelines. CONCLUSIONS: SFHCC patients with hypertension received pharmacotherapy as recommended by JNC 7 guidelines and were at the blood pressure goal set by Healthy People 2010.