Background: Health-related quality of life (HRQoL) impairment is often reported among COVID-19 ICU survivors, and little is known about their long-term outcomes. We evaluated the HRQoL trajectories between 3 months and 1 year after ICU discharge, the factors influencing these trajectories and the presence of clusters of HRQoL profiles in a population of COVID-19 patients who underwent invasive mechanical ventilation (IMV). Moreover, pathophysiological correlations of residual dyspnea were tested. Methods: We followed up 178 survivors from 16 Italian ICUs up to one year after ICU discharge. HRQoL was investigated through the 15D instrument. Available pulmonary function tests (PFTs) and chest CT scans at 1 year were also collected. A linear mixed-effects model was adopted to identify factors associated with different HRQoL trajectories and a two-step cluster analysis was performed to identify HRQoL clusters. Results: We found that HRQoL increased during the study period, especially for the significant increase of the physical dimensions, while the mental dimensions and dyspnea remained substantially unchanged. Four main 15D profiles were identified: full recovery (47.2%), bad recovery (5.1%) and two partial recovery clusters with mostly physical (9.6%) or mental (38.2%) dimensions affected. Gender, duration of IMV and number of comorbidities significantly influenced HRQoL trajectories. Persistent dyspnea was reported in 58.4% of patients, and weakly, but significantly, correlated with both DLCO and length of IMV. Conclusions: HRQoL impairment is frequent 1 year after ICU discharge, and the lowest recovery is found in the mental dimensions. Persistent dyspnea is often reported and weakly correlated with PFTs alterations. Trial registration: NCT04411459. 15D score 3 months -mean ± SD 0.857 ± 0.133 0.927 ± 0.061 0.800 ± 0.135 0.853 ± 0.114 0.637 ± 0.204 < 0.001 15D score 1 year -mean ± SD 0.880 ± 0.115 0.964 ± 0.033 0.820 ± 0.068 0.866 ± 0.088 0.572 ± 0.112 < 0.001 Mobility -mean ± SD 0.876 ± 0.207 0.963 ± 0.104 0.828 ± 0.191 0.901 ± 0.166 0.375 ± 0.298 < 0.001 Vision -mean ± SD 0.953 ± 0.119 0.992 ± 0.040 0.942 ± 0.108 0.949 ± 0.094 0.681 ± 0.280 < 0.001 Hearing -mean ± SD 0.968 ± 0.098 1.000 ± 0.000 1.000 ± 0.000 0.745 ± 0.135 0.857 ± 0.192 < 0.001 Breathing -mean ± SD 0.746 ± 0.238 0.879 ± 0.154 0.620 ± 0.227 0.753 ± 0.223 0.438 ± 0.238 < 0.001 Sleeping -mean ± SD 0.838 ± 0.238 0.940 ± 0.135 0.716 ± 0.274 0.929 ± 0.142 0.632 ± 0.312 < 0.001 Eating -mean ± SD 0.979 ± 0.102 1.000 ± 0.000 1 .000 ± 0.000 1.000 ± 0.000 0.587 ± 0.221 < 0.001 Speech -mean ± SD 0.980 ± 0.090 0.996 ± 0.032 0.996 ± 0.036 0.948 ± 0.117 0.777 ± 0.276 < 0.001 Excretion -mean ± SD 0.974 ± 0.110 1.000 ± 0.000 1.000 ± 0.000 0.872 ± 0.191 0.720 ± 0.292

C Ca ar rb bo on n d di io ox xi id de e r re es sp po on ns si iv ve en ne es ss s i in n C CO OP PD D p pa at ti ie en nt ts s w wi it th h a an nd d w wi it th ho ou ut t c ch hr ro on ni ic c h hy yp pe er rc ca ap pn ni ia a G. Scano*, A. Spinelli*, R. Duranti*, M. Gorini**, F. Gigliotti**, P. Goti*, J. Milic-Emili † Carbon dioxide responsiveness in COPD patients with and without chronic hypercapnia. G. Scano, A. Spinelli, R. Duranti, M. Gorini, F. Gigliotti, P. Goti, J. Milic-Emili. ©ERS Journals Ltd 1995. ABSTRACT: To ascertain whether and to what extent the reduced ventilatory response to a hypercapnic stimulus in chronic obstructive pulmonary disease (COPD) patients depends on a blunted chemoresponsiveness of central origin or to mechanical impairment, we studied two groups of COPD patients without (group A) and with (group B) chronic hypercapnia, but with similar degrees of airway obstruction and hyperinflation.The study was performed on 17 patients (9 normocapnic and 8 hypercapnic). Six age-matched normal subjects (group C) were also studied as a control. During a CO 2 rebreathing test, ventilation (VE), mouth occlusion pressure (P0.1), and the electromyographic activity of diaphragm (Edi) were recorded and then plotted against end-tidal carbon dioxide tension (PCO 2 ).Inspiratory muscle strength was significantly lower in the hypercapnic group (group B) compared to normocapnic group (A), and in these groups compared to the control group (C). Both patient groups exhibited significantly lower ∆VE/∆PCO 2 than the control group. In hypercapnics, ∆P0.1/∆PCO 2 was significantly lower than in normocapnics and control group, whilst mouth occlusion pressure as % of maximal inspiratory pressure ∆P0.1(%MIP)/∆PCO 2 did not differ significantly among the three groups. ∆Edi/∆PCO 2 increased from C to A. At a PCO 2 of 8.65 kPa, VE was similar in the normocapnic and control group, but lower in hypercapnics; Edi was similar in hypercapnic and control group; but greater in normocapnics. P0.1(%MIP) did not differ significantly among groups.Although these data seem to suggest that CO 2 chemoresponsiveness was normal in hypercapnic and increased in normocapnic COPD patients, the lower VE at a PCO 2 of 8.65 kPa casts doubts about the adequacy of chemoresponsiveness in the hypercapnic group. In the latter, the reduced P0.1 response in face of normal P0.1(MIP) and Edi responses to carbon dioxide stimulation could suggest an impairment in inspiratory muscle function. Mechanical impairment and inadequate chemoresponsiveness are both likely to contribute to the low ventilatory response to CO 2 stimulation in chronic hypercapnic COPD patients. Eur Respir J., 1995, 8, 78-85

Background-Pyridostigmine, an acetylcholinesterase antagonist, is useful in improving respiratory function in patients with myasthenia gravis. More recently, plasma exchange has been employed in myasthenia gravis because it acts presumably by removal of circulating antibodies against acetylcholine receptors. Surprisingly, comparative data on the effects of pyridostigmine and plasma exchange on lung volumes, respiratory muscle strength, and ventilatory control system in patients with myasthenia gravis are lacking. Methods -Nine consecutive patients with grade Ilb myasthenia gravis were studied under control conditions and after a therapeutic dose of pyridostigmine. In a second study the patients were re-evaluated a few days after a cycle of plasma exchange, before taking pyridostigmine. In each subject pulmonary volumes, inspiratory (MIP) and expiratory (MEP) muscle force, and respiratory muscle strength, calculated as average MIP and MEP as percentages of their predicted values, were measured. The ventilatory control system was evaluated in terms of volume (tidal volume, VT) and time (inspiratory time, TI, and total time, TTOT) components of the respiratory cycle. Mean inspiratory flow (VT/TI) -that is, the "driving" -and TI/TToT -that is, the "timing" -components ofventilation were also measured.Results -In each patient treatment relieved weakness and tiredness, and dyspnoea grade was reduced with plasma exchange. Following treatment, vital capacity (VC) increased on average by 9-7% with pyridostigmiine and by 14% with plasma exchange, and MIP increased by 18% and 26%, respectively. In addition, with plasma exchange but not with pyridostigmine forced expiratory volume in one second (FEV1) increased by 16% and MEP increased by 24-5%, while functional residual capacity (FRC) decreased a little (6-8%). The change in respiratory muscle strength was related to change in VC (r2 = 0.48). With plasma exchange, VT increased by 18*6% and VT/TI increased by 13-5%, while neither TI nor TIrrTOT changed.Conclusions -Plasma exchange can be used in patients with myasthenia gravis when symptoms are not adequately controlled by anticholinesterase agents. Plasma exchange increases respiratory muscle force and tidal volume due to changes in "driving" but not "timing" of the respiratory cycle.

Background -High neural drive to the respiratory muscles and rapid and shallow breathing are frequently observed in patients with chronic obstructive pulmonary disease (COPD), and both mechanical and chemical factors are thought to play a part. However, the interrelation between these factors and the modifications in the control of breathing are not clearly defined. PPLmax ratios, appears to be the major determinant of changes in breathing pattern and inspiratory muscle activity (decrease in EMG).

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