ABSTRACT
PAP is an ultra‐rare disease in which surfactant components, that impair gas exchange, accumulate in the alveolae. There are three types of PAP. The most frequent form, primary PAP, includes ...autoimmune PAP which accounts for over 90% of all PAP, defined by the presence of circulating anti‐GM‐CSF antibodies. Secondary PAP is mainly due to haematological disease, infections or inhaling toxic substances, while genetic PAP affects almost exclusively children. PAP is suspected if investigation for ILD reveals a crazy‐paving pattern on chest CT scan, and is confirmed by a milky looking BAL that gives a positive PAS reaction indicating extracellular proteinaceous material. PAP is now rarely confirmed by surgical lung biopsy. WLL is still the first‐line treatment, with an inhaled GM‐CSF as second‐line treatment. Inhalation has been found to be better than subcutaneous injections. Other treatments, such as rituximab or plasmapheresis, seem to be less efficient or ineffective. The main complications of PAP are due to infections by standard pathogens (Streptococcus, Haemophilus and Enterobacteria) or opportunistic pathogens such as mycobacteria, Nocardia, Actinomyces, Aspergillus or Cryptococcus. The clinical course of PAP is unpredictable and spontaneous improvement can occur. The 5‐year actuarial survival rate is 95%.
Purpose
The SARS-CoV-2 infection can lead to a severe acute respiratory distress syndrome (ARDS) with prolonged mechanical ventilation and high mortality rate. Interestingly, COVID-19-associated ARDS ...share biological and clinical features with sepsis-associated immunosuppression since lymphopenia and acquired infections associated with late mortality are frequently encountered. Mechanisms responsible for COVID-19-associated lymphopenia need to be explored since they could be responsible for delayed virus clearance and increased mortality rate among intensive care unit (ICU) patients.
Methods
A series of 26 clinically annotated COVID-19 patients were analyzed by thorough phenotypic and functional investigations at days 0, 4, and 7 after ICU admission.
Results
We revealed that, in the absence of any difference in demographic parameters nor medical history between the two groups, ARDS patients presented with an increased number of myeloid-derived suppressor cells (MDSC) and a decreased number of CD8
pos
effector memory cell compared to patients hospitalized for COVID-19 moderate pneumonia. Interestingly, COVID-19-related MDSC expansion was directly correlated to lymphopenia and enhanced arginase activity. Lastly, T cell proliferative capacity in vitro was significantly reduced among COVID-19 patients and could be restored through arginine supplementation.
Conclusions
The present study reports a critical role for MDSC in COVID-19-associated ARDS. Our findings open the possibility of arginine supplementation as an adjuvant therapy for these ICU patients, aiming to reduce immunosuppression and help virus clearance, thereby decreasing the duration of mechanical ventilation, nosocomial infection acquisition, and mortality.
Abstract
Background
Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body ...mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF.
Methods
Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m
2
) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression.
Results
In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (− 283.3 SE 22.4, − 207.9 20.9 and − 104.5 21.4 in patients with BMI < 25 kg/m
2
, ≥25 to < 30 kg/m
2
and ≥ 30 kg/m
2
, respectively). Nintedanib reduced the rate of FVC decline versus placebo in all subgroups by BMI, with a consistent treatment effect across subgroups (interaction
p
= 0.31). In the placebo group, the mean rate of FVC decline was numerically greater in patients with > 5% than ≤5% weight loss over 52 weeks (− 312.7 SE 32.2 versus − 199.5 SE 14.4 mL/year). Nintedanib reduced the rate of FVC decline versus placebo in both subgroups by weight loss, with a greater treatment effect in patients with > 5% weight loss (interaction
p
= 0.0008). The adverse event profile of nintedanib was similar across subgroups.
Conclusions
In patients with IPF, lower BMI and weight loss may be associated with faster decline in FVC. Nintedanib reduces the rate of FVC decline both in patients who lose weight on treatment and those who do not.
Trial registration
ClinicalTrials.gov
; Nos.
NCT01335464
and
NCT01335477
; URL:
www.clinicaltrials.gov
.
•Malnutrition is very frequent in idiopathic pulmonary fibrosis (IPF) patients.•Low fat-free mass index (FFMI) assessed by bioimpedance analysis (BIA) is reported in 28% of patients.•Body mass index ...(BMI) and mid-arm circumference (MAC) are independently associated with low FFMI.•A two-step nutritional assessment based on BMI, MAC, and BIA should be routinely performed in IPF patients.
Little is known about the indicators to assess malnutrition in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to determine the following: 1) the prevalence of malnutrition in IPF patients; 2) the nutritional indicators predictive of low fat-free mass (FFM) as measured by bioimpedance analysis; 3) the IPF patients’ characteristics associated with low FFM.
The IPF patients were consecutively recruited in a referral center for rare pulmonary diseases. Malnutrition was defined as a fat-free mass index (FFMI) = FFM (kg) / (height m2) <17 (men) or <15 (women). Nutritional assessment included body mass index (BMI), mid-arm circumference (MAC), triceps skinfold thickness, analogue food intake scale, and serum albumin and transthyretin. The primary endpoint was FFMI. Area under the receiver operating characteristic curve (AUC) assessed low FFMI prediction from nutritional indicators. Multivariable logistic regression determined variables associated with low FFMI.
Eighty-one patients were consecutively recruited. Low FFMI prevalence was 28% (23 of 81). BMI AUC was 0.91 (95% confidence interval CI, 0.84‒0.97) and MAC AUC was 0.85 (0.76‒0.94). Multivariable analysis associated BMI (odds ratio OR 0.26 95% CI, 0.12–0.54, P = 0.0003), male sex (OR 0.02 0.00–0.33, P = 0.005), and smoking (OR 0.10 0.01–0.75, P = 0.024) with a lower risk of malnutrition.
Malnutrition occurred in nearly one-third of IPF patients. Malnutrition screening should become systematic based on BMI and MAC, which are good clinical indicators of low FFMI. We propose a practical approach to screen malnutrition in IPF patients.
Evacuation of infected fluid in pleural infections is essential. To date, the use of an intrapleural fibrinolytic agent such as urokinase and DNase has not yet been assessed in infections managed by ...repeated therapeutic thoracentesis (RTT).
We performed a retrospective comparative study of two successive cohorts of consecutive patients with pleural infections from 2001 to 2018. Between 2001 and 2010, patients had RTT with intrapleural urokinase (RTT-U). After 2011, patients received intrapleural urokinase and DNase with RTT (RTT-UD). Data were collected through a standardized questionnaire.
One hundred and thirty-three patients were included: 93 were men and the mean age was 59 years (standard deviation 17.2). Eighty-one patients were treated with a combination of intrapleural urokinase and DNase, and 52 were treated with intrapleural urokinase only. In the RTT-UD, RTT failure occurred in 14 patients (17%) compared to 10 (19%) in the RTT-U group (P = 0.82). There was no difference between the two groups in intensive care unit admission, surgical referrals or in-hospital mortality. RTT-UD was associated with faster time to apyrexia (aOR = 0.51, 95%CI 0.37-0.72), a reduced length of hospital stay (aOR = 0.61, 95%CI 0.52-0.73) and a higher volume of total pleural fluid retrieved (aOR = 1.38, 95%CI 1.02-1.88). Complications were rare with only one hemothorax in the RTT-UD group and no pneumothorax requiring drainage in either group.
Compared to urokinase only, intrapleural use of urokinase and DNase in RTT was associated with quicker defervescence, shorter hospital stay and increased volumes of pleural fluid drained. Randomized controlled trials evaluating urokinase and DNase with RTT technique would be required to confirm these results.
Sarcoidosis is a systemic granulomatous disease which carries variable outcomes. Serum protein electrophoresis is an easily accessible and routinely performed examination at diagnosis, in order to ...search for hypergammaglobulinemia, which is frequently found, and to rule out other granulomatous diseases such as common variable immunodeficiency. We aimed to assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis.
We conducted a retrospective cohort-study, at Rennes University Hospital, in which all newly diagnosed patients for whom a serum protein electrophoresis had been performed at baseline were enrolled, from 2006 to 2014. The main outcome was the need for corticosteroid treatment within 2 years from diagnosis, the secondary outcome was the occurrence of relapse among treated patients.
Eighty patients were included in the study, and 41.25% of them exhibited an elevated globulins rate. In univariate analysis, an elevated ACE level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were associated with the need for corticosteroid treatment. In multivariate analysis, only ACE elevation (OR = 1.03, IC95% 1.01-1.05, p = 0.009) and extra-pulmonary involvement (OR = 5.8, IC95% 1.4-24, p = 0.015) were significant. Immunoglobulin level was not associated with the main outcome. Regarding the secondary outcome, none of the studied features were predictive of relapse among the 34 treated patients followed for two years.
There was no relation between the immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated ACE level and the presence of initial extra-pulmonary involvement were both associated with a more severe course of the disease necessitating a corticosteroid treatment.
Highlights • CAD sensitivity is still limited for automated detection of subsolid nodules. • CAD detection rate is higher for part-solid than for pure ground-glass nodules. • Part-solid nodule ...detection is not better for nodules with larger solid component.
Highlights • We analyzed CT-features of part-solid ground glass nodules in Caucasians. • These CT-features were compared to pathology on full resection specimen. • Several CT-features can help ...differentiating invasive adenocarcinoma. • A solid component larger than 5 mm had 100% sensitivity for invasive adenocarcinoma.
Recently, a novel classification system based on tumour architecture and with high prognostic impact has been proposed for pulmonary adenocarcinomas (ADCs). For imaging-based prediction of ...histological ADC subtypes and, thus, prognosis, it is of paramount importance to investigate the correlations of radio- and histomorphological parameters. Associations between histomorphological ADC growth patterns (lepidic, acinar, papillary, micropapillary and solid) and data from pre-operative assessment by computed tomography (CT) imaging of 174 resected pulmonary ADCs were analysed. Margin configuration as well as solidity/ground glass opacity of an ADC was associated with distinct histomorphological ADC growth patterns. Solid-predominant ADCs usually had smooth margins and were also solid in CT scans, while lepidic-predominant ADCs had no predominant margin pattern, were located in the periphery, showed a positive bronchogram and were frequently associated with solidity/ground glass opacity. In addition, nonspherical tumour growth was a negative predictor of overall and disease-specific patient survival. We defined CT morphological parameters that were associated with histomorphological growth patterns of pulmonary ADCs. These data may form the basis for the development of future prognostic algorithms in the palliative setting, which include an integrated evaluation of biopsy histomorphology and CT scan morphology of nonresectable pulmonary ADC.
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