Clinical outcomes of COVID-19 in long-term care facilities for people with epilepsy.

In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March-6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth's (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes.

Airway reactivity is a determinant of bronchodilator responsiveness after methacholine-induced bronchoconstriction.

Airway hyperresponsiveness (AHR) is one of the characteristics of asthma and a risk factor for persistent airflow limitation. Poor response to bronchodilator may be a cause of persistent airflow limitation. Multiple factors may determine bronchodilator responsiveness, including airway reactivity to nonspecific bronchoconstrictive agents. If patients with AHR have poor bronchodilator responsiveness, then it could be a potential mechanism for asthma and persistent airflow limitation in these patients. The objective of this study is to assess the relationship between airway reactivity to methacholine and responsiveness to beta-agonist and beta-agonist/anticholinergic combination in a large subject population. A retrospective data analysis was undertaken of 764 consecutive subjects with > or = 20% reduction in forced expiratory volume during the first second of exhalation from total lung capacity (FEV1) after < or = 189 cumulative units of methacholine. The first 382 subjects received 3 inhalations of metaproterenol and the second 382 subjects received 3 inhalations of albuterol and ipratropium combination after > or = 20% reduction in FEV1. Bronchodilator responsiveness was measured as the percent increase in FEV1 after the treatment. Airway reactivity was assessed as the log10 of methacholine dose response slope. In a simple linear regression model, airway reactivity was significantly related to bronchodilator responsiveness. The coefficient of determination (r2) was 0.15 for the whole groups; 0.14 for metaproterenol group and 0.18 for albuterol/ipratropium combination group (all p<0.0001). The regression coefficient (beta) was 14.0 for the whole group; 14.8 and 13.2, respectively, for the two bronchodilator groups. Airway reactivity to methacholine is a determinant of airway responsiveness to both beta-agonist and beta-agonist/anticholinergic combination. Subjects with higher airway reactivity have higher bronchodilator responsiveness.

Aging does not affect beta-agonist responsiveness after methacholine-induced bronchoconstriction.

OBJECTIVES: To assess the response to an inhaled beta-agonist alone or in combination with an anticholinergic agent after methacholine-induced bronchoconstriction in four age groups. DESIGN: Retrospective analysis. SETTING: Pulmonary function laboratory in a university-affiliated hospital. PARTICIPANTS: Seven hundred sixty-four consecutive subjects with a 20% reduction or more in forced expiratory volume during the first second (FEV1) of exhalation from total lung capacity after inhaling 189 or fewer cumulative units of methacholine were included in the analysis. INTERVENTION: The first 382 subjects received three inhalations of metaproterenol (total of 1.95 mg), and the other 382 subjects received three inhalations of albuterol and ipratropium combination (total of 309 microg of albuterol and 54 microg of ipratropium) after methacholine-induced bronchoconstriction. MEASUREMENTS: The response to bronchodilators was assessed as the postbronchodilator percentage change in FEV1 and the percentage of subjects recovering to 90% or better of baseline FEV1 after the use of bronchodilator. RESULTS: The percentage change in FEV1 postbronchodilator in the elderly was similar to that of the younger subjects. The percentage of subjects who recovered to 90% or better of their baseline FEV1 postbronchodilator was also similar in the elderly and younger age groups. Response to metaproterenol was similar to that of the albuterol/ipratropium combination in all age groups (all P>.05). CONCLUSION: Aging does not affect bronchodilator response to beta-agonist after methacholine-induced bronchoconstriction. The responsiveness to beta-agonist alone is similar to the responsiveness to the combination of beta-agonist and anticholinergic agent in all age groups.

Respiratory muscle strength training with nonrespiratory maneuvers.

The diaphragm and abdominal muscles can be recruited during nonrespiratory maneuvers. With these maneuvers, transdiaphragmatic pressures are elevated to levels that could potentially provide a strength-training stimulus. To determine whether repeated forceful nonrespiratory maneuvers strengthen the diaphragm, four healthy subjects performed sit-ups and biceps curls 3-4 days/wk for 16 wk and four subjects served as controls. The maximal transdiaphragmatic pressure was measured at baseline and after 16 wk of training. Maximum static inspiratory and expiratory mouth pressures and diaphragm thickness derived from ultrasound were measured at baseline and 8 and 16 wk. After training, there were significant increases in diaphragm thickness [2.5 +/- 0.1 to 3.2 +/- 0.1 mm (mean +/- SD) (P < 0.001)], maximal transdiaphragmatic pressure [198 +/- 21 to 256 +/- 23 cmH2O (P < 0.02)], maximum static inspiratory pressure [134 +/- 22 to 171 +/- 16 cmH2O (P < 0.002)], maximum static expiratory pressure [195 +/- 20 to 267 +/- 40 cmH2O (P < 0.002)], and maximum gastric pressure [161 +/- 5 to 212 +/- 40 cmH2O (P < 0.03)]. These parameters were unchanged in the control group. We conclude that nonrespiratory maneuvers can strengthen the inspiratory and expiratory muscles in healthy individuals. Because diaphragm thickness increased with training, the increase in maximal pressures is unlikely due to a learning effect.

Ratio between forced expiratory flow between 25% and 75% of vital capacity and FVC is a determinant of airway reactivity and sensitivity to methacholine.

STUDY OBJECTIVE: The ratio between forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) and FVC is thought to reflect dysanapsis between airway size and lung size. A low FEF(25-75)/FVC ratio is associated with airway responsiveness to methacholine in middle-aged and older men. The current study was designed to assess this relationship in both male and female subjects over a broader range of ages. STUDY DESIGN: Data analysis of consecutive subjects who had a >or= 20% reduction in FEV(1) after

Clinical variables are poor selection criteria for the use of methacholine bronchoprovocation in symptomatic subjects.

OBJECTIVE: Airway hyperresponsiveness (AHR) is associated with persistent air flow limitation and accelerated FEV(1) decline. AHR can influence diagnosis, treatment, and prognosis. We assessed the value of pulmonary function variables, symptoms, and history as selection criteria for methacholine bronchoprovocation testing to detect AHR in symptomatic subjects. METHODS: Over a 4-year period we conducted a prospective study of consecutive subjects who underwent methacholine bronchoprovocation testing. Baseline pulmonary function testing (PFT) and a questionnaire were obtained prior to methacholine bronchoprovocation testing. PFT and symptom and history variables were assessed as AHR predictors in univariate and multiple logistic regression analyses for the whole group and for 4 different age groups. RESULTS: There were 530 subjects, with ages ranging from 5 to 87 years, and 232 (44%) were positive for methacholine AHR. AHR was more prevalent among subjects < or = 25 years old (59%) and > 65 years old (47%) than among the other age groups. PFT values, symptom, and history variables had different AHR predictive values among the different age groups. Symptom and history variables had no AHR predictive value among subjects < or = 25 or > 65 years old. CONCLUSIONS: Young and elderly symptomatic subjects are more likely to have methacholine AHR. None of the clinical variables we studied has significant predictive value for methacholine AHR across the age groups, so these variables are poor selection criteria for methacholine bronchoprovocation testing of symptomatic subjects. Given the high prevalence of AHR among these subjects, bronchoprovocation should be considered with all individuals who have respiratory symptoms of wheezing, cough, shortness of breath, or chest tightness.

Pulmonary function characteristics in patients with different patterns of methacholine airway hyperresponsiveness.

STUDY OBJECTIVES: The American Thoracic Society guidelines for methacholine-induced airway hyperresponsiveness include a > or = 20% reduction in FEV(1) or a > or = 40% reduction in specific airway conductance (sGaw). The objectives of the current study are to assess the concordance between these two criteria and to characterize the pulmonary function and respiratory symptoms of patients with different patterns of methacholine hyperresponsiveness. STUDY DESIGN: A prospective study of 248 consecutive patients referred for methacholine bronchoprovocation testing. RESULTS: Positive methacholine hyperresponsiveness was noted in 179 patients; 139 patients (78%) had a > or = 20% reduction in FEV(1), whereas 40 patients (22%) had a > or = 40% reduction in sGaw alone without a significant change in FEV(1). The former group had the following: (1) higher baseline lung volumes, (2) lower baseline values of FEV(1) and sGaw, (3) forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75))/FVC ratios compared to patients with a reduction in sGaw alone (0.72 +/- 0.26 vs 0.97 +/- 0.28, mean +/- SD; p < 0.0001), and (4) more frequent presence of wheezing and chest tightness (p < 0.05). CONCLUSIONS: First, a substantial number of patients have a reduction in SGaw alone in response to methacholine, and secondly, this response is seen in patients with a higher FEF(25-75)/FVC ratio. Since the FEF(25-75)/FVC ratio is thought to be an index of airway size relative to lung size, we speculate that the larger intrinsic airway size relative to lung size may explain the differences in baseline parameters and patterns of methacholine hyperresponsiveness.