Application of lung volume reduction surgery for a child with filamin A (FLNA) mutations

Diffuse lung disease in early childhood due to mutations in the filamin A gene has been recently reported. Clinical outcomes vary among individuals indicating variability in phenotype but a substantial proportion of reported cases in early life have ended up in death or lung transplantation. We recently encountered a school-aged child in whom the diagnosis of a filamin A mutation was delayed and the natural history of emphysematous lung disease was altered by serial lung volume reduction surgeries. She eventually underwent a bilateral lung transplant and we report the natural history of her disease and treatments applied herein.     

Case report: Filamin A mutation lung disease recognized in an 11-year-old child

The loss of function (LOF) due to mutations in the Filamin A (FLNA) gene may result in abnormality of the FLNA protein. Of the many clinical syndromes, this condition may produce chronic lung disease, which usually presents and is diagnosed in the infant/toddler age group. Its clinical pattern may mimic broncho-pulmonary dysplasia. It is part of the entities included in childhood interstitial lung disease group of disorders. We are herein reporting a patient that was diagnosed with FLNA-associated lung disease at 11 years of age. This case provides a unique insight into the long-term course of lung disease in this illness and broadens our understanding of the spectrum of its presentation. Although the patient had symptoms early in life, the diagnosis was not entertained because of the rarity of the disorder, its atypical and clinically mild presentation, and discontinuous care due to parents moving to different cities for employment reasons. Her presentation to our institution was for pneumonia. Due to highly unusual chest X-ray images, asthenia, and early clubbing, an extensive workup included further imaging and a lung biopsy. The final diagnosis was confirmed by the detection of FLNA LOF gene mutation.     

Unclassifiable interstitial lung disease: A review

Accurate classification of interstitial lung disease (ILD) requires a multidisciplinary approach that incorporates input from an experienced respirologist, chest radiologist and lung pathologist. Despite a thorough multidisciplinary evaluation, up to 15% of ILD patients have unclassifiable ILD and cannot be given a specific diagnosis. The objectives of this review are to discuss the definition and features of unclassifiable ILD, identify the barriers to ILD classification and outline an approach to management of unclassifiable ILD. Several recent studies have described the characteristics of these patients; however, there are inconsistencies in the definition and terminology of unclassifiable ILD due to limited research in this population. Additional studies are required to determine the appropriate evaluation and management of patients with unclassifiable ILD.     

Respiratory bronchiolitis associated interstitial lung disease (RB-ILD) presenting with haemoptysis

Respiratory bronchiolitis associated interstitial lung disease is an uncommon condition in current or ex-smokers. The presentation is non-specific, but haemoptysis is uncommonly reported in this condition. We report the case of a 25-year-old woman who presented with significant haemoptysis, dyspnoea, reduced transfer factor and normal clinical examination. In addition, a Medline literature search was performed to review the clinical features and prognosis of this disease. Other causes of haemoptysis were excluded with extensive investigation. The diagnosis was made on thoracoscopic lung biopsy. The patient had significant postoperative complications of prolonged air leak and hydropneumothorax requiring further surgery and prolonged hospital stay. Advice regarding smoking cessation was given. Her pulmonary physiology remains abnormal on follow up but symptoms have improved. Respiratory bronchiolitis-ILD may present with normal examination and radiology. Haemoptysis in this case may have been associated with the underlying disease but could have been incidental. Diagnosis, in general, requires lung biopsy. As in this patient, lung function does not appear to improve significantly on follow up.     

Approach to the diagnosis of interstitial lung disease

Interstitial lung diseases (ILDs) encompass a wide range of diffuse pulmonary disorders, characterized by a variable degree of inflammatory and fibrotic changes of the alveolar wall and eventually the distal bronchiolar airspaces. ILDs may occur in isolation or in association with systemic diseases. The clinical evaluation of a patient with ILD includes a thorough medical history and detailed physical examination; obligatory diagnostic testing includes laboratory testing, chest radiography, and high-resolution computed tomography and comprehensive pulmonary function testing and blood gas analysis. To optimize the diagnostic yield, a dynamic interaction between the pulmonologist, radiologist, and pathologist is mandatory.     

Pediatric interstitial lung disease revisited

The spectrum of pediatric interstitial lung disease (PILD) includes a diverse group of rare disorders characterized by diffuse infiltrates and disordered gas exchange. Children with these conditions typically present with tachypnea, crackles, and hypoxemia. Recent advances have been made in the identification of different types of PILD that are unique to infancy. More exciting has been the discovery of genetic abnormalities of surfactant function, now described in both children and adults. A systematic evaluation of the child presenting with diffuse infiltrates of unknown etiology is essential to the diagnosis. Most often, lung biopsy is required. Current treatment options remain less than satisfactory, and morbidity and mortality remain considerable.     

21例间质性肺疾病合并肺癌临床分析

目的探讨间质性肺疾病合并肺癌的临床特点和治疗方法,提高对疾病的诊治水平。方法回顾性分析21例间质性肺病合并肺癌患者的一般资料、临床表现、实验室和特殊检查以及治疗方法。结果21例患者中男性17例,女性4例,年龄51~88岁,中位年龄65岁,15例有吸烟史。临床表现主要为咳嗽、咳痰、活动后气急。胸部CT主要表现为两肺纤维条索及网格影、蜂窝肺样改变合并结节、团块影。病理类型为腺癌47.6%,鳞癌23.8%,小细胞癌28.6%。3例以ILD起病的患者在发现肺癌前,100%NSE升高,66.7%CYFRA21-1升高,33.3%CEA升高。在同时发现ILD和肺癌的18例患者中,50%NSE升高,55.6%CYFRA21-1升高,66.1%CEA升高,16.7%SCC升高。15例接受含铂双药联合化疗,3例接受手术治疗,3例接受最佳支持治疗。5例在治疗过程中出现肺部感染。结论间质性肺疾病合并肺癌临床处置困难,对于以ILD起病的患者,在随访过程中应密切随访血清肿瘤标记物及胸部CT,使ILD-LC得以早期诊断和治疗。治疗过程中易并发肺部感染及间质性肺疾病急性加重。治疗时应对治疗的风险和获益进行充分的评估,并且给予严密的监测。     

RA-ILD与临床和实验室指标相关性研究

目的收集类风湿关节炎合并肺间质病变(RA-ILD)患者的相关临床指标、实验室指标和肺部影像学表现等临床资料,分析这些因素与RA-ILD的发生和发展的关系,为RA-ILD的诊疗提供一定的临床依据。方法回顾性收集2014年1月-2015年1月在新疆维吾尔自治区人民医院风湿免疫科住院的RA患者,一般资料、临床表现、实验室指标和影像学检查。结果 1 204例RA患者中44例发生ILD,占21.6%。6例胸闷、气短;6例有咳嗽、咳痰;6例听诊有Velcro音。比较发现RA-ILD组咳嗽咳痰、胸闷气短、Velcro音的发生率高于单纯RA组(P0.05)。RA-ILD组患者肺HRCT最常见的表现是磨玻璃影。2 RA-ILD组的平均病程、年龄明显大于单纯RA组(P0.05)。3 RA-ILD组白细胞、血红蛋白、血小板、DAS28、ESR、CRP、C3、C4、RF、GPI较单纯RA组差异无统计学意义(P0.05)。4 RA-ILD组抗CCP抗体滴度显著大于单纯RA组(P0.05)。5比较两组AKA阳性率差异有统计学意义(P0.05),而抗SSA抗体阳性率、抗核抗体阳性率差异无统计学意义(P0.05)。结论 RA-ILD患者年龄大、平均病程长,大部分临床表现不明显,需及时完善HRCT,早期诊断和治疗。高抗CCP抗体滴度、ANA阳性可能与RA-ILD的发生相关。     

Outcomes of patients with interstitial lung disease referred for lung transplant assessment

Background: Patients with interstitial lung disease (ILD) very frequently die before the opportunity to receive lung transplantation (LTx). This retrospective study describes the clinical course of 86 patients with ILD referred for LTx assessment between January 1999 and December 2002. Aims: (i) To describe the outcomes, (ii) to identify reasons of delay to transplantation, (iii) to describe the causes of death/complications and (iv) to assess the pathological diagnosis and concordance with explanted lung pathology. Methods: Data were collected from the case notes of all patients with ILD referred to the Alfred Hospital over a 4‐year period. Results: Twenty women and 66 men, mean age of 55 ± 8 years, were referred for LTx assessment. Forty‐five patients were deemed not suitable for LTx and 41 were listed. Twenty‐two patients underwent transplantation, 16 died on the waiting list and 7 are still on the waiting list. Complications were frequent (e.g. pulmonary embolism, malignancy and infection) and carried high mortality. Patients dying on the waiting list appeared generally to be in accelerated decline, dying shortly after listing, with no evidence in their lung function test assessment predicting them as a poor prognosis group. Conclusions: Serious complications and death on the waiting list of patients with idiopathic pulmonary fibrosis are high, not apparently because of delayed referral but usually in patients undergoing very rapid decline.     

Chloroquine treatment of interstitial lung disease in children

Seven children aged 3 months to 11 years with histologically confirmed interstitial lung disease (ILD) [6 with desquamative interstitial pneumonitis (DIP) and 1 with chronic interstitial pneumonitis] were treated with chloroquine, 10 mg/kg/day. One patient, diagnosed late in the course of the disease, died after three weeks of treatment, despite the addition of systemic corticosteroids. Another patient responded to combined therapy with chloroquine and prednisone and had a normal lung biopsy after 6 months of treatment. He underwent surgical repair of mitral valve stenosis and died after extensive brain infarction. The other 5 patients responded well to chloroquine therapy with major improvement in oxygenation within a few weeks and in lung function over the next few months. They remained well clinically and physiologically, including a normal response to incremental exercise, during a mean follow-up period of 9.8 years (range 3.5 to 15.7 years). None of the patients has developed retinopathy or any other ocular complication. Bronchoalveolar lavage was a useful tool for evaluation of the activity of the disease (predominance of neutrophils) in 3 out of 4 patients. We suggest that chloroquine should be considered as an effective treatment in ILD in children. Incremental exercise test may be helpful for routine follow-up and evaluation of the efficacy of a specific treatment. Pediatr Pulmonol. 1994;18:356–360. ©1994 Wiley-Liss, Inc.     

IgG4相关间质性肺疾病

IgG4相关间质性肺疾病的提出是基于对系统性IgG4相关硬化性疾病的研究发现.IgG4相关间质性肺疾病的诊断需要临床医师结合临床-影像学-病理学特征疑及此病.IgG4相关间质性肺疾病对糖皮质激素治疗反应良好,监测随访对于发现复发是必要的.