Therapeutic plasma exchange for persistent encephalopathy associated with Covid-19.

Patients infected with COVID-19 virus, show a highly variable symptomatology which can include central nervous system (CNS) dysfunction. One of the most disabling CNS manifestations is persistent severe encephalopathy seen for weeks after the resolution of the acute viral pneumonia and associated acute systemic illnesses. The precise pathophysiology of this persistent Post COVID Encephalopathy is unknown but may involve direct viral invasion of microvascular endothelium, microvascular thrombosis, toxic neuronal effects of inflammatory products, vasoactive pathology at arteriolar level or leptomeningeal inflammation. Currently, there are no established specific treatments for Post COVID -19 encephalopathy. We present a case series of three patients that underwent Therapeutic Plasma Exchange (TPE) with salinized albumin that suggests a positive therapeutic effect. We believe that the results warrant further evaluation for the role of TPE with a prospective randomized trial in persistent Post COVID -19 encephalopathy syndrome.

Two ATS recommended protocols for administration of methacholine are not equal.

BACKGROUND: The 1999 American Thoracic Society methacholine challenge guidelines stated that the 5-breath dosimeter method of methacholine administration is similar to the 2-minute tidal breath method. Recent data has disputed this assertion. We examined the differences in the diagnosis of asthma using these two methods. METHODS: Data were abstracted from a prospectively generated pulmonary function database over 4 years. During the first 2 years the 5-breath dosimeter method was used, and the subsequent 2 years the 2-minute tidal breath method was used. The effect of the delivery technique was assessed by crude and adjusted odds ratios, controlling for known confounders and group differences. RESULTS: A total of 907 subjects underwent methacholine challenge testing during the 4-year study period: 19.3% of the subjects tested with the 5-breath dosimeter method and 31.2% of those tested with the 2-minute tidal breathing method had a PC20 16.0 mg/mL) was also altered by the differences between the testing techniques. Using the 5-breath dosimeter method, 72.4% of subjects were ruled out for airway hyper-responsiveness, whereas only 59.9% of subjects were ruled out with the 2-minute tidal breathing technique (p < 0.001). CONCLUSION: The two recommended protocols for the diagnosis of asthma are not equivalent and significantly alter the rate of diagnosis of asthma as well as the severity. The differences were seen across all PC20 levels, from those with strongly positive tests (PC20 16.0 mg/mL).

Predictive value of sGaw, FEF(25-75), and FEV1 for development of asthma after a negative methacholine challenge test.

BACKGROUND: A 20% change in forced expiratory volume in 1 second (FEV(1)) during methacholine challenge testing (MCT) is a reliable marker of asthma. When the FEV(1) decrease is < 20%, there is controversy whether other changes in flows and conductance may be useful. We conducted this study to determine whether changes in sGaw, FEF(25 - 75), and FEV(1) in a negative MCT could predict future occurrence of asthma over a 3-year period. METHODS: A total of 100 consecutive patients with clinical suspicion of asthma but who had a negative MCT per ATS FEV(1) criteria (< 20% FEV(1) decline at 16 mg/mL of methacholine) performed by the 5-breath dosimeter method were analyzed. Two pulmonary fellows, blinded to MCT results, reviewed the patients' medical records. Patients were classified into one of three categories: asthmatic, unclear, and not asthmatic. Decreases in sGaw, FEF(25 - 75), and FEV(1) in the five groups were then retrieved. Analysis of variance (ANOVA) was used for data analysis. RESULTS: Of 100 patients, 23 were excluded owing to lack of a 3-year follow-up. After complete data review, the number of patients (n) in each group was as follows: asthmatic (n = 15), unclear (n = 7), and not asthmatic (n = 55). sGaw and FEF(25 - 75) decreases from the negative MCT could not predict asthma; however, decreases in FEV(1) were associated with future asthma occurrence (sGaw p = 0.21, FEF25-75 p = 0.07, FEV(1) p = 0.0009). Forty-three percent of the patients who had a 10% to 20% decline in FEV(1) eventually developed asthma. CONCLUSION: Up to 20% of patients who have symptoms suggestive of asthma but a negative MCT can still develop asthma. Declines in sGaw and FEF(25 - 75) in a negative MCT appear to have no clinical significance. A decrease in FEV(1), especially 10% to 20%, is associated with the diagnosis of future asthma.