Assessment of respiratory function and exercise tolerance at 4-6 months after COVID-19 infection in patients with pneumonia of different severity.

BACKGROUND: The evaluation of COVID-19 systemic consequences is a wide research field in which respiratory function assessment has a pivotal role. However, the available data in the literature are still sparse and need further strengthening. AIM: To assess respiratory function 4-6 months after hospital discharge based on lung disease severity in patients who overcome COVID-19 pneumonia. METHODS: Patients hospitalised either in the Internal Medicine Department (IMD) for moderate to severe disease or in the Intensive Care Unit (ICU) for critical disease underwent spirometry with maximal flow-volume curve, lung volumes, lung diffusion capacity (DLCO ) and six-minute walking test (6-MWT). RESULTS: Eighty-eight patients were analysed: 40 from the IMD and 48 from the ICU. In both cohorts, there was a greater prevalence of male patients. In the IMD cohort, 38% of patients showed at least one altered respiratory parameter, while 62% in the ICU cohort did so (P < 0.05). Total lung capacity (TLC) and DLCO were the most frequently altered parameters: 15% and 33% from IMD versus 33% and 56% from ICU, respectively (P < 0.05). In IMD patients, 5% had only restrictive deficit, 22% had only lung diffusion impairment and 10% had both. In ICU patients, 6% had only restrictive deficit, 29% had only lung diffusion impairment and 27% had both (P < 0.05). ICU patients showed a higher frequency of abnormal 6-MWT (P < 0.05). CONCLUSION: Lung function tests and 6-MWT are highly informative tools for monitoring the negative consequences of COVID-19 pneumonia, which were more frequent and more complex in patients discharged from ICU.

Single-breath oxygen dilution for the measurement of total lung capacity: technical description and preliminary results in healthy subjects.

Objective. Total lung capacity (TLC) assessment outside of a research laboratory is challenging. We describe a novel method for measuring TLC that is both simple and based only on portable equipment, and report preliminary data in healthy subjects.Approach. We developed an open circuit system to administer a known amount of oxygen to a subject in a single maximal inspiratory maneuver. Oxygen fraction, expired and inspired flows were continuously monitored to allow a precise computation of the mass balance. Values of TLC and functional residual capacity (FRC) were compared with standard methods (body plethysmography and multiple-breath helium dilution). Twenty healthy subjects participated to the study, eleven of which performed the maneuver twice to assess test-retest reliability.Main results.There was high agreement in TLC between the proposed method and the two standard methods (R2 > 0.98, bias not different from 0, and 95% limits of agreements <± 0.4 l for both). Test-retest reliability was high (intraclass correlation coefficient >0.99 and no bias). Results were similar for FRC, with a slightly higher variability due its sensitivity to changes in posture or breathing pattern.Significance.Single-breath oxygen dilution is accurate and reliable in assessing TLC and FRC in healthy subjects. The technique is appealing for time- or resource-limited settings, such as field physiological research expeditions or mass screenings.

Methods for Measuring Lung Volumes: Is There a Better One?

BACKGROUND: Accurate measurement of lung volumes is of paramount importance to establish the presence of ventilatory defects and give insights for diagnostic and/or therapeutic purposes. OBJECTIVES: It was the aim of this study to measure lung volumes in subjects with respiratory disorders and in normal controls by 3 different techniques (plethysmographic, dilutional and radiographic methods), in an attempt to clarify the role of each of them in performing such a task, without any presumptive 'a priori' superiority of one method above others. Patients andMethods: In different groups of subjects with obstructive and restrictive ventilatory defects and in a normal control group, total lung capacity, functional residual capacity (FRC) and residual volume were measured by body plethysmography, multi-breath helium (He) dilution and radiographic CT scan method with spirometric gating. RESULTS: The 3 methods gave comparable results in normal subjects and in patients with a restrictive defect. In patients with an obstructive defect, CT scan and plethysmography showed similar lung volumes, while on average significantly lower lung volumes were obtained with the He dilution technique. Taking into account that the He dilution technique does primarily measure FRC during tidal breathing, our data suggest that in some patients with an obstructive defect, a number of small airways can be functionally closed at end-expiratory lung volume, preventing He to reach the lung regions subserved by these airways. CONCLUSION: In all circumstances, both CT scan with spirometric gating and plethysmographic methods provide similar values of lung volumes. In contrast, the He dilution method can measure lower lung volumes in some patients with chronic airflow obstruction.

Tidal airway closure during bronchoconstriction in asthma: usefulness of lung volume measurements.

BACKGROUND: The presence and extent of tidal airway closure is not routinely assessed in asthma. The objective of this study was to provide a simple functional tool able to detect tidal airway closure during bronchoconstriction in asthma. METHODS: In 20 subjects with mild persistent asthma, we sequentially performed the measurement of functional residual capacity (FRC) by body plethysmography (pleth) and multibreath helium dilutional technique (He) and then computed residual volume (RV) and total lung capacity (TLC) at baseline, at the end of methacholine (MCh) challenge and after bronchodilator (albuterol). MEASUREMENTS AND MAIN RESULTS: Despite substantial bronchoconstriction (fall in FEV(1) = 35 ± 7%), TLC,pleth did not change following MCh challenge, but FRC,pleth because of dynamic pulmonary hyperinflation (+0.68 ± 0.54 L) and RV,pleth because of air trapping (+0.65 ± 0.37 L), invariably increased (on average by 22% and 46%, respectively). In contrast, FRC,He (and RV,He and TLC,He) could either increase, as seen in 13 subjects (Group I), or decrease, as seen in 7 subjects (Group II). Hence, the difference between FRC,pleth and FRC,He (Diff. FRC,pleth - FRC,He) was much greater in Group II (1.03 ± 0.41 L) than in Group I (0.22 ± 0.20 L) (p < .01). No functional differences were found between the two groups, including baseline PD(20)FEV(1) and absolute and percent change in forced vital capacity (FVC) at the end of the MCh challenge. CONCLUSIONS: Comparison between FRC,pleth and FRC,He is useful to identify asthmatics prone to tidal airway closure during MCh-induced bronchoconstriction and Diff. FRC,pleth - FRC,He can be used to measure the overall unventilated lung volume upstream of the airways closed at end-expiratory lung volume (EELV).

Diagnostic flow chart for targeted detection of alpha1-antitrypsin deficiency.

BACKGROUND: Alpha1-antitrypsin (AAT) deficiency is under-recognized, probably because many individuals affected show no clinical impairment. The targeted detection is a tool to increase its recognition. METHODS: We prospectively submitted to AAT serum levels determination, phenotyping and, if doubtful, genotyping: (i) patients with the early onset of emphysema, emphysema in absence of recognized risk or pneumothorax (path P), antineutrophil cytoplasm antibodies (ANCA) positive vasculitis (path V), cervical artery dissection (path A), Periodic acid-Schiff (PAS) positive bodies in the liver cell or unexplained abnormal transaminase level (Path L) [index cases: IC] and (ii) subjects with low-serum alpha1-globulin (path e) and close relatives of patients with AAT deficiency (path r) [non index cases: NIC]. We determined and compared gender, age, AAT serum levels values, the ratio between AAT deficiency subjects identified and all subjects examined (identified/examined). Receiver operating characteristic (ROC) curve was plotted to find the best threshold for AAT serum levels. RESULTS: Two hundred and eighty-five individuals were examined and 211 with AAT deficiency identified: 66 were IC and 145 NIC. The ratio identified/examined resulted 0.74. A serum level of 120 mg/dL was able to identify AAT deficiency with a specificity of 73% and a sensitivity of 97%. IC showed male prevalence (P=0.005), more advanced age (P=0.02), lower AAT serum levels (P=0.008). CONCLUSIONS: Our protocol is effective to detect AAT deficiency in a selected population. About 120 mg/dL (nephelometric method) is a reliable AAT serum level cut-off for selecting subjects/patients to submit to phenotype or genotype; as compared to NIC, IC are older, mostly male and with lower AAT serum levels.