Pulmonary pathology of amyotrophic lateral sclerosis patients with non-invasive ventilation, a retrospective institute-based study
Creators: name: Kiyonobu Komai
name: Ishida, Chiho
name: Takahashi, Kazuya
name: Atsuro Tagamli
name: Motozaki, Yuko
name: Atsuhiro Kawashima
Publisher: name: F1000 Research Limited
Year: 2018

description: Background<br>  In the advanced stage of amyotrophic lateral sclerosis (ALS), most patients with ALS develop respiratory insufficiency. Non-invasive ventilation (NIV) is commonly regarded to be effective to treat respiratory insufficiency in ALS and improves survival and quality of life. But there are few autopsy reports which described pathological pulmonary conditions of ALS patients with NIV support (ALS-NIV). <br> We provide long-term medical care for severely disabled neuromuscular disease patients as a neuromuscular-disease center hospital in Hokuriku area of Japan. We had also developed multidisciplinary respiratory care team for ALS. It is necessary to understand how NIV affect on lung of ALS-NIV to improve our team interventions. So, we planed retrospective hospital-based study of pathological changes in lung from ALS-NIV. <br> <br>Objective<br> We performed retrospective hospital-based post-mortem study to clarify the clinical features and pulmonary pathology of ALS-NIV patients. <br> <br>Methods<br>  To elucidate the clinical feature of pathologically confirmed ALS, we retrospectively reviewed medical records of 94 consecutive autopsied patients between 2008 and 2016. Pathological diagnosis was confirmed when the following two histopathological features were observed. First of them was systematic both upper and lower motor neuronal degeneration, and second was the existence of TDP-43 inclusion body pathology and/or Bunina bodies. <br> <br>Results<br>  We collected 45 pathologically diagnosed ALS from 92 autopsied brain. Nine ALS-NIV patients were identified from those 45 ALS. One case was excluded because it only had brain specimen.<br>  Clinical and pathological profiles of our ALS-NIV are summarized on Table. Female to male ratio was 1 to 7. Average age of death was 66.6 y.o. and median survival was 50.0 months. Mean survival time was 57.4 months. According to initial symptom, 4 cases were upper limb onset, 3 cases were bulbar onset, and a case was lower limb onset. Age of onset ranged from 50 to 77 years old, and age of death ranged from 52 to 80 years old. <br>  Right lung weight ranged from 270g to 935g, and left lung weight were from 300g to 870g. Lungs from ALS-NIV autopsy tended to be heavier than the lung which didn't undergo mechanical ventilation support. There was positive correlation between right lung weight and left lung weight (<i>r</i>=0.40). And there was weak negative correlation (<i>r</i>=-0.24) between NIV support duration and left lung weight.<br>  Seven out of 8 ALS-NIV patients had bronchopneumonia, and 5 of these 7 patients had severe bronchopneumonia. Lung congestion were observed in 2 ALS-NIV. Lung abscess were found in 1 case. There were no pulmonary embolism in this series. <br> <br>Discussion and Conclusion<br>  From this institute-based retrospective study, NIV support could improve prognosis of ALS patients. However, it would be difficult to avoid bronchopneumonia in the end stage of ALS-NIV.<br>  There were still few reports which described relation between mechanical ventilation and pathological situation of the lung from ALS. Pulmonary pathology which we showed by this post-mortem study could be useful findings to improve respiratory management of ALS-NIV. <br> <br>Acknowledgment<br>  This study was approved by the institutional review board of the Iou Hospital, National Hospital Organization of Japan.<br> This work was supported in part by grants from the Ministry of Health, Labor and Welfare of Japan. <br> <br>References	Heffernan C, Jenkinson C, Holmes T, Macleod H, Kinnear W, Oliver D, Leigh N, Ampong MA. Management of respiration in MND/ALS patients: an evidence based review. Amyotroph Lateral Scler. 7(1):5-15, 2006.	Burkhardt C, Neuwirth C, Sommacal A, Andersen PM, Weber M. Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS)? A post-mortem study of 80 ALS patients. PLoS One. May 23;12(5):e0177555. doi: 10.1371/journal.pone.0177555. eCollection 2017. 	 Hazenberg A, Kerstjens HA, Prins SC, Vermeulen KM, Wijkstra PJ. Is chronic ventilatory support really effective in patients with amyotrophic lateral sclerosis? J Neurol. 263(12):2456-2461, 2016.