Leticia Kawano-Dourado

Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD). METHODS: This was a retrospective study of patients with interstitial lung disease (ILD), positive antinuclear antibody (ANA) results (≥ 1/320), with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD). RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynauds phenomenon. The most prevalent autoantibodies in this group were ANA (89%) and anti-SSA (anti-Ro, 27%). The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05). Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

Acute Respiratory Failure in Idiopathic Pulmonary Fibrosis: Co-Infection With H1n1 And Cytomegalovirus: An Unexpected Common Denominator

We described a case of persistent influenza AH1N1 and cytomegalovirus respiratory infection in a patient with chronic interstitial lung disease and multiple bilateral pulmonary opacities. An open lung biopsy revealed diffuse organizing alveolar damage, necrotizing bronchiolitis, necrotizing pneumonia and alveolar hemorrhage, compatible with H1N1 infection as well as usual interstitial pneumonia. Diagnoses of an idiopathic CD4+ T cell lymphocytopenia and immunoglobulin G deficiency were made as an unexpected co-denominator of H1N1 and CMV persistent infection changing our treatment approach.

Low- Versus High-chloride Content Intravenous Solutions for Critically Ill and Perioperative Adult Patients: A Systematic Review and Meta-analysis

BACKGROUND: To assess whether use of low-chloride solutions in unselected critically ill or perioperative adult patients for maintenance or resuscitation reduces mortality and renal replacement therapy (RRT) use when compared to high-chloride fluids. METHODS: Systematic review and meta-analysis with random-effects inverse variance model. PubMed, Cochrane library, EMBASE, LILACS, and Web of Science were searched from inception to October 2016. Published and unpublished randomized controlled trials in any language that enrolled critically ill and/or perioperative adult patients and compared a low- to a highchloride solution for volume maintenance or resuscitation. The primary outcomes were mortality and RRT use. We conducted trial sequential analyses and assessed risk of bias of individual trials and the overall quality of evidence. Fifteen trials with 4067 patients, most at low risk of bias, were identified. Of those, only 11 and 10 trials had data on mortality and RRT use, respectively. A total of 3710 patients were included in the mortality analysis and 3724 in the RRT analysis. RESULTS: No statistically significant impact on mortality (odds ratio, 0.90; 95% confidence interval, 0.69–1.17; P = .44; I2 = 0%) or RRT use (odds ratio, 1.12; 95% confidence interval, 0.80–1.58; P = .52; I2 = 0%) was found. Overall quality of evidence was low for both primary outcomes. Trial sequential analyses highlighted that the sample size needed was much larger than that available for properly powered outcome assessment. CONCLUSIONS: The current evidence on low- versus high-chloride solutions for unselected critically ill or perioperative adult patients demonstrates no benefit, but suffers from considerable imprecision. We noted a limited exposure volume for study fluids and a relatively low risk of the populations in each study. Together with the relatively small pooled sample size, these data leave us underpowered to detect potentially important differences. Results from well-conducted, adequately powered randomized controlled trials examining sufficiently large fluid exposure are necessary.

In Situ Evidence of Pulmonary Endothelial Activation in Patients with Granulomatosis with Polyangiitis and Systemic Sclerosis

IntroductionThe aim of this study was to investigate the in situ pulmonary endothelial activation in lung lesions of granulomatosis with polyangiitis (GPA) and systemic sclerosis (SScl).MethodsWe examined the endothelial expression of ICAM-1, VCAM-1, and E-selectin using immunohistochemistry on formalin-fixed, paraffin-embedded sections of lung lesions of GPA, interstitial lung disease associated with SScl and controls.ResultsA significantly enhanced expression of ICAM-1 and E-selectin was observed in GPA and SScl pulmonary endothelium compared to controls. VCAM-1 was more pronouncedly expressed in GPA compared to SScl.ConclusionThese observations are an evidence of in situ pulmonary vascular endothelial activation in lesions of GPA and SScl, adding information to the pathogenic knowledge of both diseases.

Effects of perioperative statin use on cardiovascular complications in patients submitted to non-cardiac surgery: protocol for a systematic review, meta-analysis, and trial sequential analysis

BackgroundPreliminary evidence suggests statins may reduce major perioperative vascular events. However, evidence is limited to observational studies, underpowered trials, and non-comprehensive systematic reviews. This review aims to assess the effects of perioperative statin use on cardiovascular complications in patients submitted to non-cardiac surgery.MethodsWe will search MEDLINE/PubMed, EMBASE, LILACS, CENTRAL, Web of Science, and CINAHL for randomized controlled trials assessing the effects of perioperative statin use in adults undergoing non-cardiac surgery and reporting cardiovascular complications. For patients already using statins for hyperlipidemia, a preoperative loading dose of statin is required in the experimental group. We will place no language or publication restriction on our search. Teams of two reviewers will independently assess eligibility and risk of bias, and will extract data from the included trials. Our primary outcome is a combination of cardiovascular mortality or non-fatal myocardial infarction. We will also assess the following outcomes: individual components of the primary outcome, all-cause mortality, total myocardial infarction, elevated troponin in the first seven postoperative days, total stroke, total venous thromboembolism, postoperative atrial fibrillation, elevation of creatine phosphokinase or liver enzymes, and rates of myalgia or rhabdomyolysis. We will conduct meta-analyses using random-effects model and will use trial sequential analysis to establish monitoring boundaries to limit global type I error due to repetitive testing for our primary outcome. We will rate the quality of evidence using the GRADE system.DiscussionThe results of this systematic review may help to inform clinical practice and also the design of future large-scale randomized trials.Systematic review registrationPROSPERO CRD42016035987

Pneumonia intersticial usual: um padrão ou uma doença? Reflexão sobre o assunto

There are many ways in which a set of biological variables (clinical, laboratory, or histological variables) can characterize a distinct disease. In modern medicine, a nosological entity is most commonly determined by the primary factor responsible for the disease. Nevertheless, when the etiologic factor is unknown, a syndromic approach is the surrogate approach for establishing a diagnosis. The Brazilian Thoracic Association Guidelines for Interstitial Lung Diseases(1) have recently been published. In conformity with the official 2011 American Thoracic Society Statement, idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, being limited to the lungs, and being associated with the histopathological/ radiological pattern of usual interstitial pneumonia (UIP), the diagnosis of IPF requiring the exclusion of other forms of interstitial pneumonia.(1,2) It is a syndromic approach to diagnosis, given that the essential etiologic factor remains unknown. Typically, guidelines on a given subject gather the most relevant information available at the time, providing an excellent opportunity for a critical analysis of the subject in question. In this context, we would like to spark off a debate by asking the following question: would UIP be considered a disease in its own right if the accumulated evidence were viewed in a different light? Because UIP has such a peculiar histological pattern, chest HRCT is able to predict the histological features of UIP with a great degree of confidence in some typical cases, dispensing with a biopsy.(2) The uniqueness of UIP is determined by the process of fibrosis formation (peripheral, with temporal and spatial heterogeneity, and minimal inflammation). It is a maladaptive repair process regardless of whether it is idiopathic or related to other diseases.(3) This unique fibrotic process is designated IPF when it is not associated with other diseases. However, from a nosological point of view, the real difference between UIP related to other conditions (such as collagen vascular diseases and hypersensitivity pneumonitis) and its “idiopathic” form is unclear. We should now turn back to our initial considerations. When proposing that UIP be considered a disease in its own right, we took into consideration the characteristics that define a nosological entity. The histological features of UIP are distinctive enough to characterize a disease: • A disease of the lung repair process, UIP results in a peculiar form of fibrotic deposition, regardless of its relationship with other diseases (such information, i.e., the context in which this occurs, being of minor importance). • This peculiar form of fibrotic deposition can be diagnosed by histology and chest HRCT. All of the abovementioned features are sufficient to characterize a disease in modern medicine, although the complete pathogenesis of UIP has yet to be fully understood. Indeed, caution must be exercised when providing UIP with such a diagnostic power; correct recognition of UIP is imperative. It can be difficult for pathologists to differentiate between UIP and other, UIP-like, lesions in some cases.(4) A UIP-like pattern commonly has special features, including inflammation outside areas of honeycombing,(5) centrilobular fibrosis,(6) fewer areas of honeycombing,(7) higher scores for lymphoid hyperplasia,(5) and germinal centers.(7) Accurate differentiation between UIP and UIP-like lesions should be pursued diligently because UIP-like Usual interstitial pneumonia: a pattern or a disease? A reflection upon the topic

Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis: methodological concerns.

We read with great interest the article by Kreuter et al. [1] describing the unfavourable effects of anticoagulants in a pooled analysis of idiopathic pulmonary fibrosis (IPF) patients randomised to the placebo arm from the ASCEND (Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis) and CAPACITY (Clinical Studies Assessing Pirfenidone in Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes) trials [2, 3]. In this pooled analysis, IPF anticoagulant users differed significantly from nonusers in almost every important baseline characteristic: anticoagulant users were older (age 71.1±6.8 versus 66.9±7.5 years, p=0.0025) and they also had a higher prevalence of cardiovascular disease (43.8% versus 25.8%, p=0.0259), chronic renal failure (9.4% versus 2.9%, p=0.0419), pulmonary embolism (15.6% versus 0.2%, p<0.0001), pulmonary hypertension (9.4% versus 2.7%, p=0.0324), atrial fibrillation (46.9% versus 2.4%, p=0.0001) and deep vein thrombosis (28.1% versus 1.4%, p<0.0001). Therefore, IPF anticoagulant users started off with an increased risk of death simply due to the higher prevalence of baseline cardiovascular comorbidities. The question whether medically indicated anticoagulants are harmful to IPF patients still remains unanswered http://ow.ly/KU3Y302SEMQ

Lymphadenopathy and fever in a chef during a stay in Europe

This case illustrates a rare presentation (as lymphadenopathy and fever) of one of the most common zoonotic diseases worldwide-brucellosis-in a 22-year-old Brazilian male (a chef) who had recently returned to Brazil after having lived in and traveled around Europe for one year. The histopathology, clinical history, and response to treatment were all consistent with a diagnosis of brucellosis, which was confirmed by PCR in a urine sample. We also review some aspects of brucellosis, such as the clinical features, diagnosis, and management.

Environmental exposure in inflammatory myositis

Dear Editor We read with interest the article “Occupational exposure in patients with the antisynthetase syndrome” by LabiruaIturburu et al. [1]. The study compared a group of myositis patients with aSA (antisynthetase antibody) with a group of myositis patients without aSA. Among antisynthetase syndrome (ASS) patients, 50 % had high occupational exposure to gases, biological or mineral dust before the onset of the disease, whereas 22 % of myositis patients without aSA had such exposure (p<0.05) [1]. Despite the retrospective nature of the study, the value of the data collected is remarkable because it leads to an important conclusion: that environmental exposure could play a role in the pathogenesis of some cases of aSA-associated interstitial lung diseases, and improvement in lung function can be observed with avoidance of the offending agent. Our group has also hypothesized that, in susceptible individuals, there might be a link between inhalation of certain antigens and development of ASS. But other than occupational exposure, domiciliary exposure seems to be also a potential offending agent triggering autoimmunity. Indeed, we recently reported two well-documented ASS cases where it was observed development of a lymphocytic interstitial lung disease (ILD) associated to significant domiciliary exposure to a known inhaled offending antigen—mold and birds—and negative autoantibodies. Those cases were first interpreted as hypersensitivity pneumonitis. Only after 14 and 30 months they presented systemic symptoms compatible with ASS and anti-Jo-1 became positive [2]. Using similar methods to Labirua-Iturburu, we also submitted 118 patients with polymyositis, dermatomyositis or ASS to a semistructured questionnaire evaluating household exposure to mold, birds, and feather pillow (Table 1). Interestingly, we found a relevant environmental exposure in 70 (59 %) of the cases, and in the subgroup of 23 patients with pulmonary involvement as an opening feature of autoimmunity, the presence of substantial environmental exposure was particularly high (74 % of cases). The difference between them, however, did not reach statistic significance [3]. It is know that in susceptible individuals, the inhalation of environmental antigens may cause an inflammatory reaction, specifically, hypersensitivity pneumonitis, which is characterized by the presence of NK cells and CD8+ lymphocytes, known to be rich in granzyme B, a feature that is also found in antisynthetase syndrome [4, 5]. In the alveolar epithelial cells, a more immunogenic form of Jo-1 is significantly enriched as compared to other tissues such as the muscle. Furthermore, Jo-1 expressed in the lung is described as immunogenic due to its higher susceptibility to cleavage by granzyme B, a cytotoxic serine protease found in cytoplasmic granules of CD8 T lymphocytes and natural killer (NK) cells that play an important role in inducing apoptotic changes in target cells. Jo-1 cleavage by granzyme B has the capacity to generate fragments that have the potential to become autoantigens, therefore triggering autoimmunity [6, 7]. Based on our observations, we have come to a very similar conclusion to dr. Labirua-Iturburu, which is that an initiating inflammatory stimulus that would be capable of damaging alveolar epithelial cells and lead to the exposure and cleavage of the immunogenic form of Histidyl-tRNA synthetase (Jo-1) found in the lungs would be a possible step in the sequence of events leading to Jo-1 autoimmunity. However, we propose that the offending agent may be within the individual’s home, not only at workplace [2, 3]. Finally, the authors suggest that improvement in lung function could occur if exposure is ceased. We also propose that disease flare-ups can be observed in cases in which there is maintenance of the initiating stimulus (the A. N. Costa (*) : L. Kawano-Dourado :C. R. R. Carvalho : R. A. Kairalla Pulmonary Division, Heart Institute (InCor), Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil e-mail: nathan.andre@gmail.com

A 67-year-old woman with fever, multiple lung opacities, visual impairment and acute respiratory failure

A 67-year-old woman presented to the emergency room in acute respiratory failure. She had a 4-month history of dry cough, fever, intense fatigue, progressive dyspnoea and recent visual impairment. Her prior medical history included a mitral valve replacement in 2005 due to post-endocarditis mitral regurgitation. On examination, the patient was in hypoxemic acute distress. She was intubated and mechanically ventilated. A chest x-ray (figure 1A) just prior to endotraqueal intubation revealed bilateral air space disease and high-resolution CT of the chest (figure 1B) revealed irregular nodules, bilateral areas of conglomerate masses with air bronchograms of peribronchovascular orientation surrounded by ground glass opacities and no mediastinal lymphadenopathy. Laboratory findings indicated mild normocromic and normocytic anaemia, haemoglobin 10 g/dl, lymphopenia 168 cells/mm3, C-reactive protein 157 mg/litre (0.0–3.0 mg/litre). Tests for HIV, serum cytoplasmic antineutrophil cytoplasmic antibody, antinuclear antibody and rheumatoid factor were negative. A transesophageal echocardiogram displayed a bioprosthetic mitral valve with mild stenosis, …