Natália Melo

Idiopathic pleuroparenchymal fibroelastosis: A rare but increasingly recognized entity

Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a recently described rare entity, characterized by pleural and subpleural parenchymal fibrosis and elastosis mainly in the upper lobes. The etiology and pathophysiology are unknown. The prognosis is poor, with no effective therapies other than lung transplantation. IPPFE should be properly identified so that it can be approached correctly. This report describes two clinical cases with clinical imaging and histological features compatible with IPPFE.

Annexin A11 gene polymorphism (R230C variant) and sarcoidosis in a Portuguese population

A recent genome-wide association study detected a protective effect for the annexin A11 rs1049550*T allele (R230Cvariant) in susceptibility to sarcoidosis. We evaluated the association between rs1049550 C/T and sarcoidosis susceptibility, distinct disease phenotypes and evolution in a Portuguese population. We performed a case-control study of 208 patients and 197 healthy controls. Samples were genotyped for rs1049550 C/T using real-time polymerase chain reaction. The frequency of the annexin A11 rs1049550*T allele was significantly lower in patients than in controls (33.2 vs 44.9%, P < 0.001). Odds ratio of 0.52 and 0.44 were obtained, respectively for carriers of one (CT) and two (TT) copies normalized to the CC wild-type genotype (P < 0.001). There were no significant differences in patients with and without Löfgren syndrome. A significant increase in the frequency of the T allele was observed in patients with bronchoalveolar lavage (BAL) fluid neutrophilia (P = 0.04). No significant associations were seen for lung function pattern, radiological stages or different forms of disease evolution. Our study confirms that rs1049550*T allele exerts a significant protective effect on sarcoidosis susceptibility. Given the role of annexin A11 in cell division, apoptosis and neutrophil function, this polymorphism may affect key elements of granulomatous and interstitial inflammation in sarcoidosis.

Open lung biopsy in patients on mechanical ventilation with suspected diffuse lung disease.

BACKGROUND While open lung biopsy (OLB) performed in patients on mechanical ventilation (MV) with diffuse lung diseases (DLD) can be extremely important in establishing the diagnosis, the associated risk of this procedure should be taken into account. AIM To determine the diagnostic yield, therapeutic changes, complications and mortality in patients with DLD on MV submitted to OLB. METHODS Retrospective study of 19 patients admitted to S. João Hospital between January 1999 and July 2007 (8.5 years). Data analysed included demographic data, ventilation variables before and after biopsy, diagnostic yield, effect on subsequent treatment changes and complications of OLB. Statistical analysis was performed using SPSS 14.0. RESULTS The mean age of patients was 58+/-16.3 years old and 53% were male. The mean duration of hospital stay in Intensive Care Unit before performing OLB was 13+/-7 days. All biopsies were performed by thoracotomy. The diagnostic yield was 95%. There were no significant differences in partial pressure of arterial oxygen/fraction of inspired oxygen (PaO(2)/ FiO(2)) ratio and the positive end expiratory pressure (PEEP) before and after OLB. Postoperative complications occurred in 4 patients (21%; persistent air leak). Alteration in the diagnosis occurred in 14 patients (74%) and in 8 patients (42%) there was a modification in the treatment regimen. Global mortality was 47% (9 patients) but there were no biopsy-related deaths. CONCLUSION The high diagnostic yield and the low incidence of complications make OLB a useful procedure in patients on MV with DLD of unknown aetiology. However, early OLB may lead to even better results in some patients.

Idiopathic pulmonary fibrosis in the era of antifibrotic therapy: Searching for new opportunities grounded in evidence

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease that up to now has been associated with a poor prognosis. However, the results of the INPULSIS and ASCEND trials and the approval of nintedanib and pirfenidone have marked the beginning of a new era for IPF patients. Questions remain, however. Should these drugs be used earlier? What effect will they have on more severe disease? Will their effects last beyond the trial period? This manuscript is the outcome of a multidisciplinary meeting between pulmonology, radiology, and pathology clinicians on the use of antifibrotic agents in IPF. In our opinion, the existing data show that pirfenidone and nintedanib slow functional decline in early stages of disease. These drugs also appear to result in therapeutic benefits when administered to patients with advanced disease at diagnosis and maintain effective over time. The data also suggest that continuing antifibrotic therapy after disease progression may confer benefits, but more evidence is needed. Early diagnosis and treatment are crucial for reducing functional decline, slowing disease progression, and improving quality of life.

Acute fibrinous and organizing pneumonia: A report of 13 cases in a tertiary university hospital.

IntroductionAcute fibrinous and organizing pneumonia (AFOP) is a rare diffuse pulmonary disease, but it is not yet known whether it is a distinct form of interstitial pneumonia or simply a reflection of a tissue sampling issue. MethodsCross-sectional evaluation of clinical and radiological findings, treatments, and outcomes for patients with histologically confirmed AFOP at a tertiary university hospital between 2002 and 2015. ResultsThirteen patients (7 women, 53.8%) with a mean ± SD age of 53.5 ± 16.1 years were included. The main symptoms were fever (69.2%), cough (46.2%), and chest pain (30.8%). All patients presented a radiological pattern of consolidation and 5 (38.5%) had simultaneous ground-glass areas. Histology was obtained by computed tomography-guided transthoracic biopsy in 61.5% of cases and by surgical lung biopsy in the remaining cases. Several potential etiologic factors were identified. Eight patients (61.5%) had hematologic disorders and 3 had undergone an autologous hematopoietic cell transplant. Two (15.4%) had microbiologic isolates, 5 (38.4%) had drug-induced lung toxicity, and 2 (15.4%) were classified as having idiopathic AFOP. In addition to antibiotics and diuretics used to treat the underlying disease, the main treatment was corticosteroids, combined in some cases with immunosuppressants. Median survival was 78 months and 6 patients (46.2%) were still alive at the time of analysis. ConclusionOur findings for this series of patients confirm that AFOP is a nonspecific reaction to various agents with a heterogeneous clinical presentation and clinical course that seems to be influenced mainly by the severity of the underlying disorder.

Azitromicina como terapêutica adjuvante na pneumonia organizativa criptogénica

There are literature data about the immunomodulatory properties of some macrolides in cryptogenic organizing pneumonia (COP) as an alternative to corticosteroids in mild disease or as adjuvant to standard therapy. A sixty-year-old female, with a controlled intrinsic asthma, presented with COP and recurrent respiratory exacerbations despite corticosteroid and immunossupressant therapy. Azithromycin (500mg, on alternate days) as an adjuvant to steroids was then started, with clinical and functional improvement and regression of lung infiltrates. Withdrawal of steroids was possible in one year, without evidence of relapse in the next six months. Azithromycin was maintained (three times per week) with no documentation of adverse side effects. This clinical case reinforces the potential role of macrolides anti-inflammatory properties in COP as corticosteroids adjuvant therapy.

Analysis of sarcoidosis in the Oporto region (Portugal)

BACKGROUND Sarcoidosis is a systemic granulomatous disease of unknown etiology. Epidemiological studies of different populations are essential because clinical presentation, organ involvement, disease severity, and prognosis vary significantly according to region and population. The aim of this study was to assess epidemiological and clinical characteristics, staging factors, and clinical course in patients with sarcoidosis from a tertiary hospital in Oporto, Portugal. METHODS A retrospective analysis of patients with sarcoidosis and at least 2 years of follow-up evaluated at the Centro Hospitalar de São João between 2000 and 2014. RESULTS We identified 409 patients with sarcoidosis (females, 58.9%; mean age at diagnosis, 38.9±13.4 years; smokers, 14.4%]. All the patients were diagnosed according to the ERS/ATS/WASOG consensus statement and 64.1% had evidence of noncaseating epithelioid cell granulomas in biopsy specimens. Bronchoalveolar lavage was performed as part of the diagnostic work-up in 289 patients and 90.2% had lymphocytosis (CD4/CD8 ratio ≥3.5 in 60.9% of cases). Exertion dyspnea, cough, and constitutional symptoms were the most common presenting symptoms; 10.1% of patients were asymptomatic, 22.8% had Löfgren syndrome, and 50.5% had extrathoracic involvement. Radiographic stages of disease according to the Scadding criteria were as follows: stage 0 (5.2%), stage I (33.7%), stage II (47.0%), stage III (8.4%), and stage IV (5.7%). Impaired respiratory function was observed in 45.6% patients and was mostly mild. Systemic treatment was administered in 58.6% of cases. Overall, 45.3% of patients experienced disease resolution. CONCLUSION The epidemiological and clinical characteristics of this cohort of patients with sarcoidosis from the Oporto region in northern Portugal revealed epidemiological and clinical characteristics that were generally similar to those described in other Western Europe populations and in the US ACCESS study. However, we found a higher proportion of patients who progressed to chronic forms.

Biópsia pulmonar cirúrgica em doentes sob ventilação invasiva e com suspeita de doença difusa do parênquima pulmonar

Background: While open lung biopsy (OLB) performed in patients on mechanical ventilation (MV) with diffuse lung diseases (DLD) can be extremely important in establishing the diagnosis, the associated risk of this procedure should be taken into account. Aim: To determine the diagnostic yield, therapeutic changes, complications and mortality in patients with DLD on MV submitted to OLB. Methods: Retrospective study of 19 patients admitted to S. Joao Hospital between January 1999 and July 2007 (8.5 years). Data analysed included demographic data, ventilation variables before and after biopsy, diagnostic yield, effect on subsequent treatment changes and complications of OLB. Statistical analysis was performed using SPSS 14.0. Results: The mean age of patients was 58 ± 16.3 years old and 53% were male. The mean duration of hospital stay in Intensive Care Unit before performing OLB was 13 ± 7 days. All biopsies were performed by thoracotomy. The diagnostic yield was 95%. There were no significant differences in partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/ FiO2) ratio and the positive end expiratory pressure (PEEP) before and after OLB. Postoperative complications occurred in 4 patients (21%; persistent air leak). Alteration in the diagnosis occurred in 14 patients (74%) and in 8 patients (42%) there was a modification in the treatment regimen. Global mortality was 47% (9 patients) but there were no biopsyrelated deaths. Conclusion: The high diagnostic yield and the low incidence of complications make OLB a useful procedure in patients on MV with DLD of unknown aetiology. However, early OLB may lead to even better results in some patients. Rev Port Pneumol 2009; XV (4): 597-611

Exacerbação aguda da fibrose pulmonar idiopática

Resumo Alguns doentes com fibrose pulmonar idiopatica (FPI) apresentam durante a sua evolucao fases de agravamento clinico sem causa conhecida, designadas como “exacerbacao aguda” ou “fase acelerada” da doenca (EA). Caracterizam-se pelo agravamento marcado da dispneia, hipoxemia e pelo aparecimento de novas opacidades pulmonares ou pelo agravamento das ja existentes no estudo imagiologico. Os achados histologicos tipicos sao o dano alveolar difuso (DAD) sobreposto a alteracoes de pneumonia intersticial usual (UIP). Esta entidade clinica associa-se a uma mortalidade elevada, nao havendo ate ao momento nenhuma terapeutica de comprovada eficacia. Os autores descrevem os casos clinicos de cinco doentes que apresentaram alteracoes clinicas, funcionais e radiologicas sugestivas de EA-FPI, assim como o tratamento efectuado e a evolucao observada, enquadrando-os na discussao das caracteristicas normalmente apresentadas por esta entidade.

Erratum to "Biópsia pulmonar cirúrgica em doentes sob ventilação invasiva e com suspeita de doença difusa do parênquima pulmonar" [Rev Port Pneumol 2009; XV(4):597-611]

Por questões alheias à nossa vontade a versão em inglês do artigo “Biópsia pulmonar cirúrgica em doentes sob ventilação invasiva e com suspeita de doença difusa do parênquima pulmonar/Open lung biopsy in patients on mechanical ventilation with suspected diffuse lung disease” (Natália Melo, Sandra Figueiredo, António Morais, Conceição Souto Moura, Paulo Pinho, Pedro Bastos, Teresa Oliveira) publicado na Rev Port Pneumol 2009; XV(4):597-611, veio acompanhada de erros importantes que desvirtuaram significativamente o original, pelo que optamos pela sua nova publicação. Pelo ocorrido, as nossas desculpas aos autores.