Pulmonary alveolar proteinosis (PAP) is a rare parenchymal pulmonary disease, characterized by the accumulation of surfactant material in alveoli. Rare cases of pulmonary alveolar proteinosis have ...been reported following the use of sirolimus. All published cases have been described following solid organ transplantation, and symptoms improved quickly after treatment's cessation.
We describe a case of PAP secondary to sirolimus treating graft-versus-host reaction in a patient who received a stem cell transplant for chronic lymphocytic leukemia. Pulmonary alveolar proteinosis was cured after stopping sirolimus without any other therapeutic management.
PAP can be a rare but serious side effect of sirolimus. It is important to rule out other causes of primary or secondary PAP before suggesting a toxic drug cause.
The main challenge is to quickly diagnose this side effect to stop exposure to the toxic agent.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Pneumocystis jiroveci pneumonia in human immunodeficiency virus (HIV)-negative immunocompromised patients is associated with high mortality rates. Although ...trimethoprim-sulfamethoxazole provides a very effective prophylaxis, pneumocystosis still occurs and may even be emerging due to suboptimal characterization of patients most at risk, hence precluding targeted prophylaxis. Methods We retrospectively analyzed all cases of documented pneumocystosis in HIV-negative patients admitted in our institution, a referral center in the area, from January 1990 to June 2010, and extracted data on their underlying condition(s). To estimate incidence rates within each condition, we estimated the number of patients followed-up in our area for each condition by measuring the number of patients admitted with the corresponding international classification diagnostic code, through the national hospital discharge database (Program of Medicalization of the Information System PMSI). Results From 1990 to 2010, 293 cases of pneumocystosis were documented, of which 154 (52.6%) tested negative for HIV. The main underlying conditions were hematological malignancies (32.5%), solid tumors (18.2%), inflammatory diseases (14.9%), solid organ transplant (12.3%), and vasculitis (9.7%). Estimated incidence rates could be ranked in 3 categories: 1) high risk (incidence rates >45 cases per 100,000 patient-year): polyarteritis nodosa, granulomatosis with polyangiitis, polymyositis/dermatopolymyositis, acute leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma; 2) intermediate risk (25-45 cases per 100,000 patient-year): Waldenström macroglobulinemia, multiple myeloma, and central nervous system cancer; and 3) low risk (<25 cases per 100,000 patient-year): other solid tumors, inflammatory diseases, and Hodgkin lymphoma. Conclusions These estimates may be used as a guide to better target pneumocystosis prophylaxis in the groups most at risk.
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), now recognised by the World Health Organization as a pandemic, emerged in late 2019 ...in China 1. Patients infected with SARS-CoV-2 can develop severe pneumonia and respiratory failure, which often require treatment in intensive care units (ICU) in Western European countries 2. Oxygen therapy and supportive care are still the main forms of therapy for SARS-CoV-2 pneumonia until suitable anti-infective therapies become available.
SARS-CoV-2 infected patients with nonhypercapnic acute hypoxaemic respiratory failure can benefit from high-flow nasal oxygen outside an ICU. The technique appears to be safe for healthcare workers and could well liberate critical ICU resources.
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A proportion of patients with interstitial lung diseases (ILDs) are at risk of developing a progressive-fibrosing phenotype, which is associated with a deterioration in lung function and early ...mortality. In addition to idiopathic pulmonary fibrosis (IPF), fibrosing ILDs that may present a progressive phenotype include idiopathic nonspecific interstitial pneumonia, connective tissue disease-associated ILDs, hypersensitivity pneumonitis, unclassifiable idiopathic interstitial pneumonia, ILDs related to other occupational exposures and sarcoidosis. Corticosteroids and/or immunosuppressive therapies are sometimes prescribed to patients with these diseases. However, this treatment regimen may not be effective, adequate on its own or well tolerated, suggesting that there is a pressing need for efficacious and better tolerated therapies. Currently, the only approved treatments to slow disease progression in patients with IPF are nintedanib and pirfenidone. Similarities in pathobiological mechanisms leading to fibrosis between IPF and other ILDs that may present a progressive-fibrosing phenotype provide a rationale to suggest that nintedanib and pirfenidone may be therapeutic options for patients with the latter diseases.This review provides an overview of the therapeutic options currently available for patients with fibrosing ILDs, including fibrosing ILDs that may present a progressive phenotype, and explores the status of the randomised controlled trials that are underway to determine the efficacy and safety of nintedanib and pirfenidone.
Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection in immunocompromised patients. Quantitative real-time PCR (qPCR) is more sensitive than microscopic examination for the ...detection of P. jirovecii but also detects colonized patients. Hence, its positive predictive value (PPV) needs evaluation. In this 4-year prospective observational study, all immunocompromised patients with acute respiratory symptoms who were investigated for PCP were included, totaling 659 patients (814 bronchoalveolar lavage fluid samples). Patients with negative microscopy but positive qPCR were classified through medical chart review as having retained PCP, possible PCP, or colonization, and their clinical outcomes were compared to those of patients with microscopically proven PCP. Overall, 119 patients were included for analysis, of whom 35, 41, and 43 were classified as having retained PCP, possible PCP, and colonization, respectively. The 35 patients with retained PCP had clinical findings similar to those with microscopically proven PCP but lower fungal loads (P < 0.001) and were mainly non-HIV-infected patients (P < 0.05). Although the mean amplification threshold was higher in colonized patients, it was not possible to determine a discriminant qPCR cutoff. The PPV of qPCR in patients with negative microscopy were 29.4% and 63.8% when considering retained PCP and retained plus possible PCP, respectively. Patients with possible PCP had a higher mortality rate than patients with retained PCP or colonization (63% versus 3% and 16%, respectively); patients who died had not received co-trimoxazole. In conclusion, qPCR is a useful tool to diagnose PCP in non-HIV patients, and treatment might be better targeted through a multicomponent algorithm including both clinical/radiological parameters and qPCR results.
Women and COPD: do we need more evidence? Gut-Gobert, Christophe; Cavaillès, Arnaud; Dixmier, Adrien ...
European respiratory review,
03/2019, Volume:
28, Issue:
151
Journal Article
Peer reviewed
Open access
The increasingly female face of chronic obstructive pulmonary disease (COPD) prevalence among women has equalled that of men since 2008, due in part to increased tobacco use among women worldwide and ...exposure to biomass fuels. This finding is supported by a number of characteristics. There is evidence of susceptibility to smoking and other airborne contaminants, along with epidemiological and phenotypic manifestations. COPD has thus become the leading cause of death in women in the USA. The clinical presentation is characterised by increasingly pronounced dyspnoea with a marked tendency towards anxiety and depression, undernutrition, nonsmall cell lung cancer (especially adenocarcinoma) and osteoporosis. Quality of life is also more significantly impacted. The theories advanced to explain these differences involve the role played by oestrogens, impaired gas exchange in the lungs and smoking habits. While these differences require appropriate therapeutic responses (smoking cessation, pulmonary rehabilitation, long-term oxygen therapy), barriers to the treatment of women with COPD include greater under-diagnosis than in men, fewer spirometry tests and medical consultations. Faced with this serious public health problem, we need to update and adapt our knowledge to the epidemiological changes.
The chemokine CXCL13 controls the normal organization of secondary lymphoid tissues and the neogenesis of ectopic lymphoid structures in nonlymphoid organs, particularly the lungs. The progression ...and severity of idiopathic pulmonary fibrosis (IPF), a fatal and irreversible interstitial lung disease, is predicted by the circulating blood concentrations of CXCL13. Although CXCL13 is produced by pulmonary tissues, it has not been determined which cells are involved. This study examines CXCL13 production by lung tissue macrophages from patients with IPF and the signaling pathways controlling CXCL13 gene expression in human alveolar macrophages (AM) and monocyte-derived macrophages (MoDM). CXCL13 is found in CD68- and CD206-positive AM from patients with IPF, and the CXCL13 gene is induced in these macrophages and MoDM when they are stimulated with LPS. We found that TNF-α and IL-10 control optimal CXCL13 gene expression in MoDM and possibly in AM by activating the NF-κB and JAK/STAT pathways, respectively. We also found that blood TNF-α and CXCL13 concentrations are significantly correlated in patients with IPF, suggesting that TNF-α contributes to CXCL13 production in humans. In conclusion, the results of this study demonstrate that AM from patients with IPF produces CXCL13 and that the NF-κB and JAK/STAT pathways are required to induce the expression of this major chemokine.
•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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In ...this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice.
Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care. Patients were categorized as treated (received approved antifibrotics) or untreated (did not receive approved antifibrotics, but may have received other unapproved therapies). Classification of IPF diagnosis (confirmed/suspected) and severity ('mild'/'moderate'/'severe') for each patient was based on the individual physician's report. Patients' perspectives were not recorded in this study.
In total, 290 physicians responded to the questionnaire. Overall, 54% of patients with IPF did not receive treatment with an approved antifibrotic. More patients had a confirmed IPF diagnosis in the treated (84%) versus the untreated (51%) population. Of patients with a confirmed diagnosis, 40% did not receive treatment. The treated population was younger than the untreated population (67 vs 70 years, respectively; p ≤ 0.01), with more frequent multidisciplinary team evaluation (83% vs 57%, respectively; p ≤ 0.01). A higher proportion of untreated patients had forced vital capacity > 80% at diagnosis versus treated patients. Of patients with 'mild' IPF, 71% did not receive an approved antifibrotic versus 41% and 60% of patients with 'moderate' and 'severe' IPF, respectively.
Despite the availability of antifibrotic therapies, many European patients with confirmed IPF do not receive approved antifibrotic treatment. Importantly, there appears to be a reluctance to treat patients with 'mild' or 'stable' disease, and instead adopt a 'watch and wait' approach. More education is required to address diagnostic uncertainty, poor understanding of IPF and its treatments, and issues of treatment access. There is a need to increase physician awareness of the benefits associated with antifibrotic treatment across the spectrum of IPF severity.
The AIRBAg study was designed to assess the prevalence of chronic obstructive pulmonary disease (COPD) in dairy farmers and to define its associated risk factors.
Between March 2012 and February 2017 ...randomly selected dairy farmers in the French region of Brittany were asked to complete a self-administered questionnaire and undergo an occupational health check-up with electronic mini-spirometry and standard spirometry. Those having one or more of the following features: chronic cough, chronic bronchitis, wheezing, dyspnea and/or a ratio FEV1/FEV6 < 80% were then referred to a pulmonologist for further check-up including spirometry with a reversibility test. Each COPD case was matched with three controls (dairy farmers and non-farm employees), for sex and age ( ± 5 years). Conditional multivariate logistic regression models were used to estimate the odds ratios between COPD occurrence and various risk factors.
The 1203 farmers examined included 525 (43.6%) who were "at risk of bronchial obstruction" and 432 (35.9%) of these saw the pulmonologist. This screening identified 16 (1.3%) cases of COPD, including eight non-smokers and five with an FEV1 < 80% of predicted values. Their average age was 54.6 ( ± 7.7) years and 10 of them were men. None complained of illness before the study. Multivariate analyses revealed no significant occupational risk factors for COPD.
This unexpected result may be because Breton dairy farms began to modernize early (1950s), giving rise to conditions with much lower exposure to airborne contaminants.
•Occupational exposure could be involved in the pathophysiology of COPD.•A total of 1203 dairy farmers (Brittany, France) were screened for COPD.•Risk factors were identified by comparing COPD cases with two control populations.•Multivariate analyses revealed no significant occupational risk factors for COPD.•Farm modernization from 1950 onwards could explain this unexpected result.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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