Pauliane Vieira Santana

Rationale: Persistent dyspnea despite normal cardiopulmonary structure is a frequent but poorly understood long-term sequela of COVID-19. Scant data exist on the multidimensional clinical profiles that underlie dyspnea in this setting. Objectives: We aimed to characterize multidimensional phenotypes associated with persistent dyspnea several years after COVID-19 hospitalization. Methods: Post-hospitalization COVID-19 survivors without structural cardiopulmonary disease underwent assessment 41-47 months after acute infection, including respiratory muscle strength, diaphragm and parasternal intercostal ultrasound, exercise capacity, peripheral muscle evaluation, and patient-reported outcomes. Predefined univariate analyses examined associations with persistent dyspnea (mMRC ≥ 2) and inspiratory muscle weakness (MIP and SNIP < 70% predicted). Unsupervised hierarchical clustering followed by k-means analysis identified multidimensional clinical–functional phenotypes. Results: Of 316 screened individuals, 270 were included; 34.4% reported persistent dyspnea and 23.3% demonstrated inspiratory muscle weakness. Persistent dyspnea and inspiratory muscle weakness were associated with distinct patterns of impairment across diaphragmatic ultrasound indices, peripheral muscle strength, fatigue, and functional capacity. Multidimensional clustering identified three phenotypes: (1) a dyspnea–fatigue phenotype, predominantly affecting women with obesity, characterized by severe dyspnea, fatigue, and reduced six-minute walk distance; (2) a preserved phenotype, with near-normal function and minimal symptoms; and (3) a dyspnea–inspiratory muscle weakness phenotype, characterized by impaired inspiratory strength, altered diaphragm ultrasound indices, dyspnea with minimal fatigue, and reduced functional capacity. Conclusions: Persistent dyspnea several years after COVID-19 hospitalization reflects heterogeneous multidimensional phenotypic profiles rather than a uniform post-COVID condition. Multidimensional phenotyping may refine clinical characterization and inform targeted rehabilitation and long-term management strategies for post-hospitalization COVID-19 survivors.

Background: Thrombocytopenia is common in critically ill patients with cancer. However, the association of platelet count with spontaneous bleeding is controversial in critically ill patients and the association with cancer-related characteristics is unknown.Methods: This observational study includes patients with active cancer and severe thrombocytopenia. A logistic regression model adjusted for confounders was used to evaluate the association of daily platelet count and cancer-related characteristics (type of cancer and presence of metastasis) with spontaneous bleeding. Confounders were identified using directed acyclic graphs.Results: We screened 5822 patients, 255 (4.4%) met eligibility criteria resulting in 1401 daily observations. Fifty-three patients (20.8%) had spontaneous bleeding during the intensive care unit stay, 64% presenting minor, and 36% major bleeding. The adjusted odds ratio (OR) for spontaneous bleeding with platelet count between 49 and 20 x 10(9)/L was 4.6 (1.1-19.6), with platelet count between 19 and 10 x 10(9)/L was 14.2 (3.1-66.2), and with platelet count below 10 x 109/L was 39.6 (6.9-228.5). The adjusted OR for spontaneous bleeding in patients with hematologic malignancies was 0.6 (0.4-1.2), and 4.3 (2.0-9.0) for patients with metastatic tumor.Conclusions: In critically ill patients with active cancer and severe thrombocytopenia, lower counts of platelets and presence of metastasis are associated with increased risk of spontaneous bleeding, while hematologic malignancy is not associated with increased risk of spontaneous bleeding.

Background and objective The precise coordination of respiratory muscles during exercise minimizes work of breathing and avoids exercise intolerance. Fibrotic interstitial lung disease (f‐ILD) patients are exercise‐intolerant. We assessed whether respiratory muscle incoordination and thoracoabdominal asynchrony (TAA) occur in f‐ILD during exercise, and their relationship with pulmonary function and exercise performance. Methods We compared breathing pattern, respiratory mechanics, TAA and respiratory muscle recruitment in 31 f‐ILD patients and 31 healthy subjects at rest and during incremental cycle exercise. TAA was defined as phase angle (PhAng) >20°. Results During exercise, when compared with controls, f‐ILD patients presented increased and early recruitment of inspiratory rib cage muscle (p < 0.05), and an increase in PhAng, indicating TAA. TAA was more frequent in f‐ILD patients than in controls, both at 50% of the maximum workload (42.3% vs. 10.7%, p = 0.01) and at the peak (53.8% vs. 23%, p = 0.02). Compared with f‐ILD patients without TAA, f‐ILD patients with TAA had lower lung volumes (forced vital capacity, p < 0.01), greater dyspnoea (Medical Research Council > 2 in 64.3%, p = 0.02), worse exercise performance (lower maximal work rate % predicted, p = 0.03; lower tidal volume, p = 0.03; greater desaturation and dyspnoea, p < 0.01) and presented higher oesophageal inspiratory pressures with lower gastric inspiratory pressures and higher recruitment of scalene (p < 0.05). Conclusion Exercise induces TAA and higher recruitment of inspiratory accessory muscle in ILD patients. TAA during exercise occurred in more severely restricted ILD patients and was associated with exertional dyspnoea, desaturation and limited exercise performance.

The diaphragm is the main muscle of respiration, acting continuously and uninterruptedly to sustain the task of breathing. Diaphragmatic dysfunction can occur secondary to numerous pathological conditions and is usually underdiagnosed in clinical practice because of its nonspecific presentation. Although several techniques have been used in evaluating diaphragmatic function, the diagnosis of diaphragmatic dysfunction is still problematic. Diaphragmatic ultrasound has gained importance because of its many advantages, including the fact that it is noninvasive, does not expose patients to radiation, is widely available, provides immediate results, is highly accurate, and is repeatable at the bedside. Various authors have described ultrasound techniques to assess diaphragmatic excursion and diaphragm thickening in the zone of apposition. Recent studies have proposed standardization of the methods. This article reviews the usefulness of ultrasound for the evaluation of diaphragmatic function, addressing the details of the technique, the main findings, and the clinical applications.

Background: Fibrotic interstitial lung disease (FILD) patients are typically dyspneic and exercise-intolerant with consequent impairment of health-related quality of life (HRQoL). Respiratory muscle dysfunction is among the underlying mechanisms of dyspnea and exercise intolerance in FILD but may be difficult to diagnose. Using ultrasound, we compared diaphragmatic mobility and thickening in FILD cases and healthy controls and correlated these findings with dyspnea, exercise tolerance, HRQoL and lung function. Methods: We measured diaphragmatic mobility and thickness during quiet (QB) and deep breathing (DB) and calculated thickening fraction (TF) in 30 FILD cases and 30 healthy controls. We correlated FILD cases’ diaphragmatic findings with dyspnea, exercise tolerance (six-minute walk test), lung function and HRQoL (St. George’s Respiratory Questionnaire). Results: Diaphragmatic mobility was similar between groups during QB but was lower in FILD cases during DB when compared to healthy controls (3.99 cm vs 7.02 cm; p < 0.01). FILD cases showed higher diaphragm thickness during QB but TF was lower in FILD when compared to healthy controls (70% vs 188%, p < 0.01). During DB, diaphragmatic mobility and thickness correlated with lung function, exercise tolerance and HRQoL, but inversely correlated with dyspnea. Most FILD cases (70%) presented reduced TF, and these patients had higher dyspnea and exercise desaturation, lower HRQoL and lung function. Conclusion: Compared to healthy controls, FILD cases present with lower diaphragmatic mobility and thickening during DB that correlate to increased dyspnea, decreased exercise tolerance, worse HRQoL and worse lung function. FILD cases with reduced diaphragmatic thickening are more dyspneic and exercise-intolerant, have lower HRQoL and lung function.

Most patients with unilateral diaphragm paralysis (UDP) have unexplained dyspnea, exercise limitations, and reduction in inspiratory muscle capacity. We aimed to evaluate the generation of pressure in each hemidiaphragm separately and its contribution to overall inspiratory strength. Twenty-seven patients, 9 in right paralysis group (RP) and 18 in left paralysis group (LP), with forced vital capacity (FVC) < 80% pred, and 20 healthy controls (CG), with forced expiratory volume in 1 s (FEV₁) > 80% pred and FVC > 80% pred, were evaluated for lung function, maximal inspiratory (MIP) and expiratory (MEP) pressure measurements, diaphragm ultrasound, and transdiaphragmatic pressure during magnetic phrenic nerve stimulation (Pdi_Tw). RP and LP had significant inspiratory muscle weakness compared to controls, detected by MIP (− 57.4 ± 16.9 for RP; − 67.1 ± 28.5 for LP and − 103.1 ± 30.4 cmH₂O for CG) and also by Pdi_TW (5.7 ± 4 for RP; 4.8 ± 2.3 for LP and 15.3 ± 5.7 cmH₂O for CG). The Pdi_Tw was reduced even when the non-paralyzed hemidiaphragm was stimulated, mainly due to the low contribution of gastric pressure (around 30%), regardless of whether the paralysis was in the right or left hemidiaphragm. On the other hand, in CG, esophagic and gastric pressures had similar contribution to the overall Pdi (around 50%). Comparing both paralyzed and non-paralyzed hemidiaphragms, the mobility during quiet and deep breathing, and thickness at functional residual capacity (FRC) and total lung capacity (TLC), were significantly reduced in paralyzed hemidiaphragm. In addition, thickness fraction was extremely diminished when contrasted with the non-paralyzed hemidiaphragm. In symptomatic patients with UDP, global inspiratory strength is reduced not only due to weakness in the paralyzed hemidiaphragm but also to impairment in the pressure generated by the non-paralyzed hemidiaphragm.