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Multiple breath washout (MBW) has successfully assessed the silent lung zone particularly in cystic fibrosis lung disease, however, it is limited to the communicating lung only. There are a number of different pulmonary function methods that can assess what is commonly referred to as trapped air, with varying approaches and sensitivity. Twenty-five people with cystic fibrosis (pwCF) underwent MBW, spirometry, body plethysmography, and spirometry-controlled computed tomography (spiro-CT) on the same day. PwCF also performed extensions to MBW that evaluate air trapping, including our novel extension (MBWShX), which reveals the extent of under-ventilated lung units (UVLU). Additionally, we used 2 previously established 5-breath methods that provide a volume of trapped gas (VTG). We used trapped air % from spiro-CT as the gold standard for comparison. UVLU derived from MBWShX showed the best agreement with trapped air %, both in terms of correlation (RS 0.89, P<0.0001) and sensitivity (79%). Bland-Altman analysis demonstrated a significant underestimation of the VTG by both 5-breath methods (-249ml [95%CI -10796; 580ml] and -203ml [95%CI -997;591ml], respectively). Parameters from both spirometry and body plethysmography were sub-optimal at assessing this pathophysiology. The parameters from MBWShX demonstrated the best relationship with spiro-CT and had the best sensitivity compared to the other pulmonary function methods assessed in this study. MBWShX shows promise to assess and monitor this critical pathophysiological feature, which has been shown to be a driver of lung disease progression in pwCF.
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Background: Many survivors of severe COVID-19 pneumonia experience lingering respiratory issues. There is limited research on follow-up chest imaging findings in patients with COVID-19 ARDS, particularly in relation to their mMRC dyspnea scores and pulmonary function tests (PFTs). This study addresses this gap by investigating the clinical characteristics, mMRC dyspnea scores, PFTs, and chest CT findings of COVID-19 ARDS patients at the 6 months post-recovery. By analyzing these variables together, we aim to gain a better understanding of the long-term health consequences of COVID-19 ARDS. Methods: This prospective observational study included 56 subjects with COVID-19 ARDS with dyspnea at the six-month follow-up visits. These patients were evaluated by chest CT, mMRC dyspnea scale, and PFT. The CT severity score was calculated individually for each of the four major imaging findings - ground glass opacities (GGOs), parenchymal/atelectatic bands, reticulations/septal thickening, and consolidation - using a modified CT severity scoring system. Statistics were carried out to find any association between individual CT chest findings and the mMRC dyspnea scale and forced vital capacity (FVC). p values < 0.05 were considered statistically significant. Results: Our study population had a mean age of 55.86 ± 9.60 years, with 44 (78.6%) being men. Grades 1, 2, 3, and 4 on the mMRC dyspnea scale were seen in 57.1%, 30.4%, 10.7%, and 1.8% of patients respectively. Common CT findings observed were GGOs (94.6%), reticulations/septal thickening (96.4%), parenchymal/atelectatic bands (92.8%), and consolidation (14.3%). The mean modified CT severity scores for GGOs, reticulations/septal thickening, parenchymal/atelectatic bands, and consolidation were 10.32 ± 5.51 (range: 0-21), 7.66 ± 4.33 (range: 0-19), 4.77 ± 3.03 (range: 0-14) and 0.29 ± 0.91 (range 0-5) respectively. Reticulations/septal thickening (p = 0.0129) and parenchymal/atelectatic bands (p = 0.0453) were associated with an increased mMRC dyspnea scale. Parenchymal/atelectatic bands were also associated with abnormal FVC (<80%) (p = 0.0233). Conclusion: Six-month follow-up chest CTs of COVID-19 ARDS survivors with persistent respiratory problems showed a statistically significant relationship between increased mMRC dyspnea score and imaging patterns of reticulations/septal thickening and parenchymal/atelectatic bands; while parenchymal/atelectatic bands also showed a statistically significant correlation with reduced FVC.
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COVID-19 , Disnea , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos X , Humanos , COVID-19/diagnóstico por imagen , COVID-19/complicaciones , Masculino , Femenino , Disnea/diagnóstico por imagen , Disnea/fisiopatología , Persona de Mediana Edad , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , SARS-CoV-2 , Anciano , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/fisiopatología , Adulto , Índice de Severidad de la Enfermedad , Capacidad VitalRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a rare and progressive interstitial lung disease characterized by irreversible distortion of lung architecture and subsequent loss of pulmonary function. Pirfenidone is an antifibrotic agent associated with increased progression-free survival and overall survival rates, but it carries multiple side effects. The aim of the study was to examine the efficacy and safety profile of pirfenidone in a real-life context, with a focus on the concomitant use of antithrombotic and/or anticoagulant treatments. The clinical and functional data (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], diffusing lung capacity for carbon monoxide [DLCO], and 6 min walking test distance [6MWD]) of all IPF patients treated with pirfenidone and referred to our two centers between 2019 and 2022 were retrospectively analyzed at baseline, 6 and 12 months after the start of treatment. A total of 55 IPF subjects undergoing pirfenidone treatment were included in the analysis (45.5% females, median [IQR] age at disease onset 68.0 [10.0] years, median [IQR] age at baseline 69.0 [10.8] years). Compared to baseline, at 12 months, FVC (86.0% vs. 80.0%; p = 0.023) and DLCO (44.0% vs. 40.0%; p = 0.002) were significantly reduced, while FEV1 (p = 0.304) and 6MWD (p = 0.276) remained stable; no significant change was recorded at 6 months. Most of the reported adverse events were mild or moderate. Gastrointestinal intolerance (9.1%) was the main cause of treatment discontinuation. A total of 5% of patients reported at least one minor bleeding event, although all episodes occurred in those receiving concomitant antithrombotic or anticoagulant. Overall, this real-life experience confirms the efficacy and safety profile of pirfenidone in the case of the concomitant use of antithrombotic and/or anticoagulant drugs.
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RATIONALE: Imbalance between forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) (dysanapsis) has been reported in children who are obese. This dysanaptic growth might begin at an early age, although there are no data on children younger than 6 years. OBJETIVES: To assess whether body mass index (BMI) and early weight gain, in healthy infants born at term, plays a significant role in the imbalance between FEV1 and FVC, even in the absence of obesity. METHODS: Lung function was measured by means of raised volume rapid thoracic compression in 69 healthy infants born at term from the Nutrition in Early Life and Asthma cohort. Dysanapsis was defined as zFVC >0.674, zFEV0 .5 ≥-1.645, and FEV0 .5/FVC ≤-1.645. Weight gain (g/day) and growth rate (cm/year) were calculated as the difference between weight and length on the test date and those at birth. To assess the relationship between zBMI and dysanapsis, a receiver operating characteristic curve was performed. Multivariable analysis was carried out by means of linear regressions (one for each lung function index) and by logistic regression for dysanapsis (yes/no). RESULTS: Higher zBMI was associated with risk of dysanapsis (odds ratio: 3.53, [95% confidence interval: 1.30; 9.66]; p = .014): Each additional zBMI unit was associated with ~10 mL higher FVC and with ~3.5% lower FEV0.5/FVC. Weight gain was associated with lower FEV0.5/FVC ratio. CONCLUSION: Dysanaptic development of lung function begins very early in infancy and is related with weight gain and body mass index, even in the absence of obesity.
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INTRODUCTION: This investigation aimed to thoroughly characterize the range of pulmonary function abnormalities present in individuals with Parkinson's disease (PD) and to evaluate the effects of levodopa therapy on these respiratory dysfunctions. METHODS: Ninety-five PD patients diagnosed via the UK Parkinson's Disease Society Brain Bank Diagnostic Criteria were recruited, excluding those with a smoking history or unable to perform pulmonary function tests (PFTs). Severity was assessed using the Hoehn and Yahr Scale. Spirometry-measured PFT parameters (forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow rate (PEFR)) were compared against matched predicted values. The changes in PFT parameters post-levodopa challenge were assessed. RESULTS: Most of the PD patients were aged between 51-60 years, with a mean age of 55.89 ± 8.37 years. Of these, 65.3% were male. A significant proportion of the cohort exhibited restrictive pulmonary patterns (73.7%), while a smaller fraction displayed obstructive (7.4%) or normal (18.9%) pulmonary function patterns. Notably, levodopa treatment correlated with marked improvements in all measured PFT parameters, especially evident in the enhancements from the "off" medication stage to the "on" stage for FVC and FEV1 (P=0.0001). A weak positive correlation between the severity of respiratory restriction and the duration of PD (r = 0.139, P = 0.021) was found, suggesting that PD's progression exerts an increasingly adverse effect on respiratory function over time. CONCLUSION: The findings of this study illustrate that restrictive pulmonary abnormalities are more prevalent than obstructive patterns in PD patients and that these patients respond favorably to levodopa therapy.
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Lung underdevelopment is a rare congenital anomaly with variable clinical significance and presenting symptoms. It usually manifests during childhood. We present two cases of developmental lung anomaly subtypes and discuss clinical presentation and outcomes in such patient populations. LEARNING POINTS: Pulmonary underdevelopment is a challenging diagnosis and should be considered in patients with unilateral opacification on chest radiograph.Childhood developmental history is critical for diagnosis as delayed, or misdiagnoses are common. Definitive diagnosis can be made by computed tomography scan.Management is watchful waiting with close monitoring, with long term prognosis remaining unclear.
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The determination the forced vital capacity (FVC) and the forced expiratory volume in 1â¯second (FEV1) during spirometry studies, is at the core of the evaluation of the pulmonary function of patients with respiratory diseases. The Global Lung Function Initiative (GLI) offers the most extensive data set of normal lung functions available, which is currently used to determine the average expected/predicted FEV1 and FVC (predV), and their lower limit of normal (LLN, 5th percentile) at any given height and age for women and men. These prediction equations are currently expressed in a rather complex form: predV = exp [p+ (a x Ln (height) + (n x Ln (age)) + spline] and LLN = exp(Ln (predV) + Ln (1 - 1.645 x S x CV)/S); and are currently used to generate interpretations in commercialized spinographic system. However, as shown in this paper, these equations contain physiological and fundamental allometric information on lung volumes that become obvious when rewriting mean predicted values as a "simple" power function of height and LLN as a percentage of the mean predicted values. We therefore propose to present the equations of prediction obtained from the GLI data using simplified expressions in adults (18-95 years old) to reveal some of their physiological and allometric meaning. Indeed, when predicted FEV1 and FVC (predV) were expressed under the form predV= αx heightax b(age), the resulting exponent (a) ranges between 2 and 3, transforming the one dimension of a length (size) into a volume, akin to the third-order power (cubic) function of height historically used to predict lung volumes. Only one function, b (age), is necessary to replace all the factors related to age, including the tables of discrete data of spline functions original equations. Similarly, LLN can be expressed as LLN = c (age) xpredV to become a simple percentage of the predicted values, as a function of age. The equations with their respective new polynomial functions were validated in 52,764 consecutive spirometry tests performed in 2022 in 22,612 men and 30,152 women at the Cleveland Clinic. Using these equations, it become obvious that for both women and men, FEV1/FVC ratio decreases with the size as the exponent of the power function of height is lower for FEV1 than FVC. We conclude that rewriting the GLI predicted equations with simpler formulations restitutes to the GLI data some of their original allometric meaning, without altering the accuracy of their prediction.
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Pulmón , Adulto , Masculino , Humanos , Femenino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Volumen Espiratorio Forzado/fisiología , Valores de Referencia , Pulmón/fisiología , Capacidad Vital/fisiología , Pruebas de Función Respiratoria/métodos , Espirometría/métodosRESUMEN
Rationale: The use of race-specific reference values to evaluate pulmonary function has long been embedded into clinical practice; however, there is a growing consensus that this practice may be inappropriate and that the use of race-neutral equations should be adopted to improve access to health care. Objectives: To evaluate whether the use of race-neutral equations to assess percent predicted forced vital capacity (FVC%pred) impacts eligibility for clinical trials, antifibrotic therapy, and referral for lung transplantation in Black, Hispanic/Latino, and White patients with interstitial lung disease (ILD). Methods: FVC%pred values for patients from the Pulmonary Fibrosis Foundation Patient Registry were calculated using race-specific (Hankinson and colleagues, 1999), race-agnostic (Global Lung Function Initiative [GLI]-2012), and race-neutral (GLI-2022 or GLI-Global) equations. Eligibility for ILD clinical trials (FVC%pred >45% and <90%), antifibrotic therapy (FVC%pred >55% and <82%), and lung transplantation referral (FVC%pred <70%) based on GLI-2022 and GLI-2012 equations were compared with those based on the Hankinson 1999 equation. Results: Baseline characteristics were available for 1,882 patients (Black, n = 104; Hispanic/Latino, n = 103; White, n = 1,675), and outcomes were evaluated in 1,531 patients with FVC%pred within ±90 days of registry enrollment (Black, n = 78; Hispanic/Latino, n = 72; White, n = 1,381). Black patients were younger at the time of consent and more likely to be female compared with Hispanic/Latino or White patients. Compared with GLI-2022, the Hankinson 1999 equation misclassified 22% of Black patients, 14% of Hispanic/Latino patients, and 12% of White patients for ILD clinical trial eligibility; 21% of Black patients, 17% of Hispanic/Latino patients, and 19% of White patients for antifibrotic therapy eligibility; and 6% of Black patients, 14% of Hispanic/Latino patients, and 12% of White patients for lung transplantation referral. Similar trends were observed when comparing the GLI-2012 and Hankinson 1999 equations. Conclusions: Misclassification of patients for critical interventions is highly prevalent when using the Hankinson 1999 equation and highlights the need to consider adopting the race-neutral GLI-2022 equation for enhanced accuracy and more equitable representation in pulmonary health care. Our results make a compelling case for reevaluating the use of race as a physiological variable and emphasize the pressing need for continuous innovation to ensure equal and optimal care for all patients regardless of their race or ethnicity. Clinical trial registered with www.clinicaltrials.gov (NCT02758808).
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Trasplante de Pulmón , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Capacidad Vital , Estados Unidos , Determinación de la Elegibilidad/métodos , Pruebas de Función Respiratoria , Fibrosis Pulmonar/fisiopatología , Fibrosis Pulmonar/terapia , Fibrosis Pulmonar/etnología , Hispánicos o Latinos/estadística & datos numéricos , Sistema de Registros , Selección de Paciente , Población Blanca/estadística & datos numéricos , Negro o Afroamericano , Enfermedades Pulmonares Intersticiales/fisiopatología , Enfermedades Pulmonares Intersticiales/terapia , Enfermedades Pulmonares Intersticiales/etnología , Enfermedades Pulmonares Intersticiales/diagnóstico , Valores de ReferenciaRESUMEN
BACKGROUND: Elexacaftor in combination with Tezacaftor and Ivacaftor (ETI) became licensed in the United Kingdom in early 2022 for children aged 6-11 years with cystic fibrosis (CF) and an eligible mutation. Many in this age group have excellent prior lung health making quantitative measurement of benefit challenging. Clinical trials purport that lung clearance index (LCI2.5) measurement is most suitable for this purpose. OBJECTIVES: This study aimed to understand the clinical utility of LCI2.5 in detecting change after commencing ETI in the real world. PATIENT SELECTION/METHODS: Baseline anthropometric data were collected along with spirometry (forced expiratory volume in 1 s [FEV1], forced vital capacityFV and LCI2.5 measures in children aged 6-11 years with CF before starting ETI. Measures were repeated after a mean (range) of 8.2 (7-14) months of ETI treatment. The primary endpoint was a change in LCI2.5, with secondary endpoints including change in FEV1 and change in body mass index (BMI) also reported. RESULTS: Twelve children were studied (seven male, mean age 9.5 years at baseline). Our study population had a mean (SD) LCI2.5 of 7.01 (1.14) and FEV1 of 96 (13) %predicted at baseline. Mean (95% confidence interval) changes in LCI2.5 [-0.7 (-1.4, 0), p = .06] and BMI [+0.7 (+0.1, +1.3), p = .03] were observed, along with changes in FEV1 of +3.1 (-1.9, +8.1) %predicted. CONCLUSIONS: Real-world changes in LCI2.5 (-0.7) are different to those reported in clinical trials (-2.29). Lower baseline LCI2.5 as a result of prior modulator exposure, high baseline lung health, and new LCI2.5 software analyses all contribute to lower LCI2.5 values being recorded in the real world of children with CF.
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Aminofenoles , Benzodioxoles , Fibrosis Quística , Combinación de Medicamentos , Indoles , Pirrolidinas , Quinolonas , Humanos , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/fisiopatología , Niño , Masculino , Femenino , Aminofenoles/uso terapéutico , Quinolonas/uso terapéutico , Indoles/uso terapéutico , Volumen Espiratorio Forzado/efectos de los fármacos , Benzodioxoles/uso terapéutico , Piridinas/uso terapéutico , Pirazoles/uso terapéutico , Pulmón/fisiopatología , Pulmón/efectos de los fármacos , Pirroles/uso terapéutico , Capacidad Vital/efectos de los fármacos , Espirometría , Agonistas de los Canales de Cloruro/uso terapéuticoRESUMEN
Bacterial pore-forming toxins (PFTs) that disrupt host plasma membrane integrity (PMI) significantly contribute to the virulence of various pathogens. However, how host cells protect PMI in response to PFT perforation in vivo remains obscure. Previously, we demonstrated that the HLH-30/TFEB-dependent intrinsic cellular defense (INCED) is elicited by PFT to maintain PMI in Caenorhabditis elegans intestinal epithelium. Yet, the molecular mechanism for the full activation of HLH-30/TFEB by PFT remains elusive. Here, we reveal that PRMT-7 (protein arginine methyltransferase-7) is indispensable to the nuclear transactivation of HLH-30 elicited by PFTs. We demonstrate that PRMT-7 participates in the methylation of HLH-30 on its RAG complex binding domain to facilitate its nuclear localization and activation. Moreover, we showed that PRMT7 is evolutionarily conserved to regulate TFEB cellular localization and repair plasma damage caused by PFTs in human intestinal cells. Together, our observations not only unveil a novel PRMT-7/PRMT7-dependent post-translational regulation of HLH-30/TFEB but also shed insight on the evolutionarily conserved mechanism of the INCED against PFT in metazoans.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Proteínas de Caenorhabditis elegans , Membrana Celular , Proteína-Arginina N-Metiltransferasas , Proteína-Arginina N-Metiltransferasas/metabolismo , Membrana Celular/metabolismo , Humanos , Proteínas de Caenorhabditis elegans/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Animales , Caenorhabditis elegans/metabolismo , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidad , Metilación , Células HEK293 , Factores de Transcripción con Motivo Hélice-Asa-Hélice BásicoRESUMEN
OBJECTIVE: To describe the demographics and clinical profile of parafoveal telangiectasia (PFT) and compare risk factors for diabetic retinopathy (DR) among PFT and non-PFT patients. METHODS: This cross-sectional hospital-based study included 2,834,616 new patients presenting to a multi-tier ophthalmology hospital network in India between August 2010 and June 2021. Patients with a clinical diagnosis of PFT in at least one eye were included as cases. The data were collected using an electronic medical record system. RESULTS: Overall, 2,310 (0.081%) patients were diagnosed with PFT. Most of the patients were female (62.42%) with (odds ratio [OR] = 2.08), and had bilateral (84.85%) affliction. The most common age group at presentation was during the sixth decade of life with 825 (35.71%) patients. The overall prevalence was higher in patients from an upper socio economic status (0.242%) presenting from the metropolitan geography (0.113%; OR = 2.37). Systemic history of diabetes mellitus (DM) with a mean duration of 122.03 ± 95.59 months was seen in 849 (36.75%) and hypertension in 609 (26.36%) patients. Of the 4,270 eyes, 2,441 (57.17%) eyes had a visual impairment of mild or no visual impairment (<20/70) followed by moderate visual impairment (>20/70-20/200) in 1022 (23.93%) eyes. The risk of sight threatening diabetic retinopathy (STDR) among PFT patients was higher (OR = 1.43) compared to non-PFT cohort. Choroidal neovascular membrane (CNVM) was observed in 481 (11.26%) eyes. CONCLUSION: PFT is more common in females and is predominantly bilateral. PFT is more common in upper socio economic status and majority of the eyes had mild or moderate visual impairment. Diabetes and Hypertension are associated risk factors in PFT.
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Retinopatía Diabética , Hipertensión , Humanos , Femenino , Masculino , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Ciencia de los Datos , Registros Electrónicos de Salud , Estudios Transversales , Factores de Riesgo , Trastornos de la Visión , Demografía , Hipertensión/epidemiología , India/epidemiologíaRESUMEN
OBJECTIVE: The aim of this study is to examine whether there is a synergistic relationship between the diaphragm and pelvic floor muscles (PFM) in pregnant women. MATERIAL AND METHODS: Our study was carried out as a cross-sectional study in primigravid pregnants in the second and third trimesters. Superficial electromyography (EMG), 2D/3D ultrasonography (USG), pulmonary function test (PFT), PERFECT, maximum expiratory pressure (MEP) and inspiratory pressure (MIP) measurements were used to evaluate pelvic floor and diaphragm muscle functions during pregnancy. Mann-Whitney U test was used to show the change in the second and third trimesters, and Spearman correlation was used to determine the relationship. RESULTS: No correlation was found between the EMG data of the PFM and diaphragm, or between the USG data of the PFM and diaphragm in all participants, in the second and third trimesters. In the third trimester of the study, diaphragmatic thickness and levator hiatal area (LHA) decreased and both diaphragm and PFM % MVC EMG parameters increased. In the third trimester, FVC, MIP, MEP decreased, and nonsignificant increase in FEV1, FEV1/FVC and peak ekspiratuar flow(PEF) were detected. A significant correlation was found between pelvic floor levator hiatal area USG and FEV1/FVC in both trimesters (r: 0,577p: 0,004). CONCLUSION: There may be a synergistic relationship between the diaphragm and PFM in pregnant women, the relationship may weaken as pregnancy progresses, and there may be no coactivation relationship between the two muscles. In order to prevent the occurrence of pelvic floor dysfunction during pregnancy and to increase the effect of rehabilitation programs, the relationship between the diaphragm and the PFM should be determined and more studies should be conducted.
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Diafragma Pélvico , Mujeres Embarazadas , Femenino , Embarazo , Humanos , Contracción Muscular/fisiología , Diafragma/diagnóstico por imagen , Estudios Transversales , Electromiografía , Número de EmbarazosRESUMEN
Background: Few studies have looked at how SARS-CoV-2 affects pulmonary function, exercise capacity, and health-related quality of life over time. The purpose of this study was to evaluate these characteristics in post COVID-19 subjects 1 year after recovery. Methods: The study included two groups. The case group included post COVID-19 subjects who had recovered after a year, and the control group included healthy participants who had never tested positive for COVID-19. Results: The study screened 90 participants, 42 of whom met the eligibility criteria. The findings revealed that the majority of post COVID-19 subjects had relatively normal lung function 1-year post-recovery. A significant reduction in DLCO (B/P%) was observed in the case group vs. control. The exercise capacity test revealed a clinically significant difference in distance walked and a significant difference in the dyspnea post-walk test in the case group compared to the control group. The case group's health-related quality of life domain scores were significantly affected in terms of energy/fatigue, general health, and physical function. Conclusions: The post COVID-19 subjects were shown to have well-preserved lung function after 1 year. However, some degree of impairment in diffusion capacity, exercise capacity, and health-related quality of life remained.
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COVID-19 , Calidad de Vida , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Pulmón , Disnea/epidemiologíaRESUMEN
INTRODUCTION: Patients with COVID-19 have an increased risk for microvascular lung thrombosis. In order to evaluate the type and prevalence of perfusion defects, we performed a longitudinal analysis of combined perfusion single-photon emission and low-dose computed tomography (Q-SPECT/CT scan) in patients with COVID-19 pneumonia. METHODS: Consecutive patients with severe COVID-19 (B.1.1.7 variant SARS-CoV-2) and respiratory insufficiency underwent chest Q-SPECT/CT during hospitalization, and 3 months after discharge. At follow-up (FU), Q-SPECT/CT were analyzed and compared with pulmonary function tests (PFT), blood analysis (CRP, D-dimers, ferritin), modified Medical Research Council (mMRC) dyspnea scale, and high-resolution CT scans (HRCT). Patients with one or more segmental perfusion defects outside the area of inflammation (PDOI) were treated with anticoagulation until FU. RESULTS: At baseline, PDOI were found in 50 of 105 patients (47.6 %). At FU, Q-SPECT/CT scans had improved significantly (p < 0.001) and PDOI were recorded in 14 of 77 (18.2 %) patients. There was a significant correlation between mMRC score and the number of segmental perfusion defects (r = 0.511, p < 0.001), and a weaker correlation with DLCO (r = -0.333, p = 0.002) and KCO (r = -0.373, p = 0.001) at FU. Neither corticosteroid therapy nor HRCT results showed an influence on Q-SPECT/CT changes (p = 0.94, p = 0.74). CRP, D-Dimers and ferritin improved but did not show any association with the FU Q-SPECT/CT results (p = 0.08). CONCLUSION: Segmental mismatched perfusion defects are common in severe COVID-19 and are correlated with the degree of dyspnea. Longitudinal analyses of Q-SPECT/CT scans in severe COVID-19 may help understand possible mechanisms of long COVID and prolonged dyspnea.
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COVID-19 , Embolia Pulmonar , Humanos , SARS-CoV-2 , Tomografía Computarizada de Emisión de Fotón Único/métodos , Síndrome Post Agudo de COVID-19 , Pulmón/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Disnea , FerritinasRESUMEN
The upper and lower airways are typically subjected to identical inflammatory stimuli and comprise a single organ that is functionally connected. 40 patients with chronic rhinosinusitis with nasal polyps who had failed medical treatment and undergone FESS participated in our study. Prior to surgery and three months after surgery, nasal obstruction symptoms were measured using the NOSE score system and pulmonary function tests were evaluated using spirometry. The mean Nose Score was 70 before surgery but dropped to 4 afterward, with a p value < 0.001 showing a statistically significant improvement in the nasal symptoms following FESS. The mean pre-operative FVC, FEV1, and FEV1/FVC% values were 3.19, 2.53, and 78.81%, respectively, while the mean post-operative values were 3.14, 2.5, and 79.01%. Following FESS, there wasn't a statistically significant change in lung function tests. Our study showed that percentage of change of total NOSE score has a statistically significant Negative correlation with percentage of change of pulmonary function tests parameters. This study demonstrates the positive effects of FESS on nasal polyposis patients' quality of life and nasal obstruction symptoms without having any negative impacts on the lower airways.
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This study aims to evaluate the predictive value of routine pulmonary function testing (PFT) at the 12-month mark post-autologous hematopoietic cell transplant (AHCT) in identifying clinically significant lung disease in lymphoma survivors. In 247 patients, 173 (70%) received BEAM (carmustine, etoposide, cytarabine, melphalan), and 49 (20%) received TBC (thiotepa, busulfan, cyclophosphamide) conditioning regimens. Abnormal baseline PFT was noted in 149 patients (60%). Thirty-four patients had a significant decline (reduction of >/= 20% in DLCO or FEV1 or FVC) in post-AHCT PFT, with the highest incidence in the CNS lymphoma group (39%). The incidence of clinically significant lung disease post-transplant was low at 2% and there was no association between abnormal pre- and 1-year post-transplant PFTs with the development of clinical lung disease. While this study illustrates the impact of treatment regimens on PFT changes, it did not demonstrate a predictive value of scheduled PFTs in identifying clinically significant post-AHCT lung disease.
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Trasplante de Células Madre Hematopoyéticas , Enfermedades Pulmonares , Linfoma no Hodgkin , Linfoma , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfoma/terapia , Linfoma/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Carmustina/uso terapéutico , Etopósido/efectos adversos , Melfalán/uso terapéutico , Trasplante Autólogo , Acondicionamiento Pretrasplante/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
INTRODUCTION: Spermatogonial stem cells (SSCs) offer remarkable competencies for animal reproduction and overcoming human disease as a result of their differentiation capability. We evaluated the effect of small molecule pifithrin-mu (PFT-µ) as a well-known inhibitor of P53 on SSC biological processes such as viability, apoptosis, and gene expression pattern. METHODS: The SSCs were isolated from the testes of adult NMRI mice and then cultured in DMEM / F12 medium containing 10% FBS. Then, they were characterized by the immunocytochemistry (ICC) technique by high PLZF and low c-Kit expressions. SSCs colony formation assay was carried out and their viability was estimated by MTT (Methylthiazolyldiphenyl-tetrazolium bromide, or 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay upon exposure to PFT-µ (0, 0.6, 1.2, 2.5, and 5µM). The apoptosis percentages also were measured using FACS analysis, and finally, Oct4 and Stra8 expression at mRNA levels was assessed using real-time quantitative PCR. RESULTS: The 0.6 and 1.2µM PFT-µ improved the viability of SSC based on MTT assay results; however, 2.5 and 5µM PFT-µ reduced SSC viability compared with the control group. Moreover, PFT-µ at lower concentration enhanced the colony size of SSCs and diminished their apoptosis. As well, as exposure to PFT-µ up-regulated Oct4 expression, while down-regulating the meiotic entry marker, Stra8. CONCLUSION: Based on findings, optimized concentrations of PFT-µ can decrease SSCs apoptosis, and conversely potentiate their pluripotency and self-renewal capacities in vitro.
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INTRODUCTION: Pulmonary exacerbation (Pex) are common in pediatric primary ciliary dyskinesia (PCD), however changes in forced expiratory volume in 1 s precent predicted (FEV1pp) during Pex are not well described. AIM: To assess the evolution of FEV1pp during Pex and to define factors associated with failure to return to baseline lung function. METHOD: This was a retrospective study of patients with PCD between 2010 and 2022. Pex were defined as the presence of increased respiratory symptoms treated with intravenous (IV) antibiotics. The main outcomes were the changes in FEV1 during therapy and the proportion of patients (responders) achieving ≥90% of baseline FEV1pp values at the end of admission. RESULTS: The study included 52 Pex events in 28 children with PCD. The rate of responders was 32/41 (78%) at the end of admission. Nonresponse was associated with lower median body mass index (BMI) Z-score (-2.4 vs. -0.4, p < .01) and with a history of IV treated Pex in the previous year (p = .06). For the 22 Pex with available FEV1pp measurements at mid admission, the median relative and absolute improvement from admission to Day 7 was 9.1% and 6.2%, respectively (p- .001), and from Days 7 to 14 was 4.4% and 2.8%, respectively (p = .08). CONCLUSION: In children with PCD treated with IV antibiotics, the majority of lung function recovery happens during the first week of IV therapy. Lower BMI was associated with nonresponse to therapy.
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Trastornos de la Motilidad Ciliar , Fibrosis Quística , Humanos , Niño , Estudios Retrospectivos , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/diagnóstico , Progresión de la Enfermedad , Pulmón , Volumen Espiratorio Forzado , Antibacterianos/uso terapéuticoRESUMEN
PURPOSE: Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional regions of the lung. A phase-II, multi-center, prospective study of 4DCT-ventilation functional avoidance was completed. Pre and post-treatment pulmonary function tests (PFTs) were acquired and assessed pulmonary function change. This study aims to evaluate which clinical, dose and dose-function factors predict PFT changes for patients treated with 4DCT-ventilation functional avoidance radiotherapy. MATERIALS AND METHODS: 56 patients with locally advanced lung cancer receiving radiotherapy were accrued. PFTs were obtained at baseline and three months following radiotherapy and included forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), and FEV1/FVC. The ability of patient, clinical, dose (lung and heart), and dose-function metrics (metrics that combine dose and 4DCT-ventilation-based function) to predict PFT changes were evaluated using univariate and multivariate linear regression. RESULTS: Univariate analysis showed that only dose-function metrics and the presence of chronic obstructive pulmonary disease (COPD) were significant (p<0.05) in predicting FEV1 decline. Multivariate analysis identified a combination of clinical (immunotherapy status, presence of thoracic comorbidities, smoking status, and age), along with lung dose, heart dose, and dose-function metrics in predicting FEV1 and FEV1/FVC changes. CONCLUSION: The current work evaluated factors predicting PFT changes for patients treated in a prospective functional avoidance radiotherapy study. The data revealed that lung dose- function metrics could predict PFT changes, validating the significance of reducing the dose to the functional lung to mitigate the decline in pulmonary function and providing guidance for future clinical trials.
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Neoplasias Pulmonares , Pulmón , Humanos , Neoplasias Pulmonares/radioterapia , Estudios Prospectivos , Respiración , Pruebas de Función RespiratoriaRESUMEN
Among patients with COPD, ventilatory inefficiency in response to exercise can be due to respiratory muscle dysfunction or expiratory flow limitation causing air-trapping and dynamic hyperinflation. We discuss a case of severe ventilatory limitation in response to exercise due to reduced respiratory muscle mass in the setting of gender-affirming hormone therapy (GAHT), and how the interpretation of pulmonary function testing (PFT) and respiratory symptoms among transgender and gender diverse (TGD) patients can be influenced by GAHT.