For patients with amyotrophic lateral sclerosis (ALS), variables such as age, diagnostic delay, forced vital capacity, bulbar symptoms, and ALS Functional Rating Scale-Revised scores are significantly associated with higher risk of respiratory insufficiency or death at 6 months after presentation. Using these findings, researchers created and validated a prognostic model with the goal of using the model in a clinical setting to predict a 6-month risk of respiratory failure onset and therefore help in treatment decisions, according to a publication in the European Respiratory Journal.
Researchers created and internally validated the prognostic model using a single-center cohort of patients with ALS, and then externally validated the model using 23 phase 2/3 clinical trials from the Pooled Resource Open-Access ALS Clinical Trials database. Respiratory insufficiency was defined as initiating noninvasive ventilation, having a forced vital capacity <50% of predicted, having a tracheostomy placed, or death. The prognostic model was created using a multivariable logistic regression to calculate associations between baseline characteristics and respiratory insufficiency.
Of the 765 patients with ALS included in this study, 58% were men, 87% were white, the average baseline forced vital capacity was 81%, the mean baseline ALS Functional Rating Scale-Revised score was 37, and 39% had respiratory insufficiency 6 months after presentation.
Patients who developed respiratory insufficiency were significantly older when diagnosed, had a shorter diagnosis delay, higher ALS El Escorial criteria, higher bulbar symptom onset, lower forced vital capacity, and lower ALS Functional Rating Scale scores, compared with those who did not have respiratory insufficiency.
After multivariable analysis, age at diagnosis, diagnosis delay, symptom onset site, forced vital capacity, ALS Functional Rating Scale-Revised total score, and ALS Functional Rating Scale-Revised dyspnea score were retained as predictors for the prognostic model. Internal validation indicated a sensitivity of 83%, a specificity of 81%, a positive predictive value of 77%, and a negative predictive value of 86%.
Of the 7083 patients from the Pooled Resource Open-Access ALS Clinical Trials database, 62% were men, 96% were white, the average baseline forced vital capacity was 88%, and the mean baseline ALS Functional Rating Scale-Revised score was 37, and 35% had respiratory insufficiency 6 months after presentation. The external validation indicated a c-statistic of 0.74 (95% CI, 0.72-0.75), a sensitivity of 53%, a specificity of 82%, the Hosmer-Lemeshow goodness-of-fit test signified a value of P <.001, and standardized Pearson X² test signified a value of P =.001.
Limitations of this study include a decreased c-statistic, sensitivity, and negative predictive value from the cohort of patients to the Pooled Resource Open-Access ALS Clinical Trials database, potential bias from heterogeneity in the Pooled Resource Open-Access ALS Clinical Trials database, and the incidences of the individual outcomes differed between the 2 study groups.
The researchers concluded “[a] clinician can use our clinical prognostic rule to estimate a -month risk of respiratory failure onset, thus facilitating referrals and respiratory interventions.”
Ackrivo J, Hansen-Flaschen J, Wileyto EP, Schwab RJ, Elman L, Kawut SM. Development of a prognostic model of respiratory insufficiency or death in amyotrophic lateral sclerosis [published online February 6, 2019]. Eur Respir J. doi:10.1183/13993003.02237-2018