Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP) represents a group of lung disorders caused by the inhalation of a wide variety of organic particles by susceptible individuals. HP occurs mainly in nonsmokers, but smoking may promote an insidious and chronic disease. The prevalence of HP is difficult to estimate accurately since several antigens can produce the disease, but the range spans infancy to old age. Regardless of the causative antigen or its environmental setting, the clinical manifestations are essentially the same. Three different clinical presentations have been recognized: acute, subacute, and chronic. In the acute form, patients show flu-like symptomatology, followed by dyspnea and dry cough. Symptoms subside a few hours or days later. The subacute and chronic forms result from recurrent low-level antigen exposure and are characterized by progressive dyspnea and dry cough. Other constitutional symptoms such as fatigue, anorexia, and weight loss can be apparent. Fever may occur in the subacute form. Importantly, chronic HP may evolve insidiously or may result from repeated acute/subacute episodes. Recurrent acute, subacute, and chronic HP may progress to irreversible lung fibrosis or provoke emphysematous changes.HP can be difficult to identify, and precise diagnosis requires a history of exposure and a constellation of clinical, imaging, laboratory, bronchoalveolar lavage and pathologic findings. General laboratory tests show an increase of acute phase reactants. Specific precipitating antibodies, when present, are evidence of antigen exposure, and are a hallmark for diagnosis. Chest radiograph usually reveals widespread ground-glass attenuation, and nodular or reticulonodular shadowing. High-resolution CT features include diffuse or patchy ground-glass opacities with small poorly defined nodules and air trapping. Pulmonary function tests are characterized by a predominantly restrictive ventilatory defect with loss of lung volume and hypoxemia at rest that worsens with exercise. Bronchoalveolar lavage reveals a significant increase in lymphocytes, mostly over 40%. In the acute form there is also an increase in neutrophils. Antigen-induced lymphocyte proliferation, and environmental or laboratory-controlled inhalation challenge, may be used for diagnostic purposes and can help to establish a diagnosis of insidious forms of HP. In subacute or chronic cases, lung biopsy may be necessary. Typical findings include bronchiolitis, lymphocytic alveolitis, and loosely formed granulomas, although occasionally other morphologic patterns such as nonspecific interstitial pneumonia may exist. Treatment focuses on avoiding further exposure to the offending antigen(s). Corticosteroids are recommended in subacute and chronic forms. The usual regimen consists of initial high doses of systemic corticosteroid (e.g. prednisone 0.5-1.0 mg/kg/day), followed by gradual tapering.     

Hypersensitivity pneumonitis: insights in diagnosis and pathobiology

Hypersensitivity pneumonitis (HP) is a complex syndrome resulting from repeated exposure to a variety of organic particles. HP may present as acute, subacute, or chronic clinical forms but with frequent overlap of these various forms. An intriguing question is why only few of the exposed individuals develop the disease. According to a two-hit model, antigen exposure associated with genetic or environmental promoting factors provokes an immunopathological response. This response is mediated by immune complexes in the acute form and by Th1 and likely Th17 T cells in subacute/chronic cases. Pathologically, HP is characterized by a bronchiolocentric granulomatous lymphocytic alveolitis, which evolves to fibrosis in chronic advanced cases. On high-resolution computed tomography scan, ground-glass and poorly defined nodules, with patchy areas of air trapping, are seen in acute/subacute cases, whereas reticular opacities, volume loss, and traction bronchiectasis superimposed on subacute changes are observed in chronic cases. Importantly, subacute and chronic HP may mimic several interstitial lung diseases, including nonspecific interstitial pneumonia and usual interstitial pneumonia, making diagnosis extremely difficult. Thus, the diagnosis of HP requires a high index of suspicion and should be considered in any patient presenting with clinical evidence of interstitial lung disease. The definitive diagnosis requires exposure to known antigen, and the assemblage of clinical, radiologic, laboratory, and pathologic findings. Early diagnosis and avoidance of further exposure are keys in management of the disease. Corticosteroids are generally used, although their long-term efficacy has not been proved in prospective clinical trials. Lung transplantation should be recommended in cases of progressive end-stage illness.     

Circulating MicroRNAs: a Potential Biomarker for Cardiac Damage,Inflammatory Response,and Left Ventricular Function Recovery in Pediatric Viral Myocarditis

Viral myocarditis (VM) can be a life-threatening event resulting in cardiac failure, chronic cardiomyopathy, and death. VM typically includes three phases, i.e., acute, subacute, and resolution/chronic. We prospectively investigated cardiac- and inflammatory-associated plasma-circulating miRNA levels in eight pediatric patients with VM during the three stages of the disease. The level of cardiac-associated miR-208a was significantly elevated during the acute phase compared with the subacute and resolution/chronic phases. The level of cardiac- and inflammatory-associated miR-21 was significantly elevated during the acute phase compared to the resolution/chronic phase. Moreover, cardiac-associated miR-208b levels during the subacute phase correlated with systolic left ventricular function recovery as measured during the resolution/chronic phase. The findings of our study demonstrate an association between cardiac damage and the inflammatory response and the expression of miR-208a and miR-21 during the pathological progression of myocarditis. We also found that miR-208b levels exhibit a prognostic significance for left ventricular functional recovery.     

Imaging-Guided Therapies for Pericardial Diseases

Frequently, multimodality imaging is indispensable in the care of patients with pericardial disease. With cardiac magnetic resonance imaging, pericardial inflammation can be characterized as acute, subacute, or chronic. This spectrum of inflammation is variably associated with reduced compliance of the pericardium, which may result in constrictive pathophysiology, typically well-defined with echocardiography. This interplay between inflammation and hemodynamics is often optimally characterized with multimodality imaging and has redefined the approach of pericardiologists to diagnose, prognosticate, and tailor individual therapies.     

SARS: radiological features

Air-space disease is typical in severe acute respiratory syndrome (SARS) and may be indistinguishable from pneumonia of other causes. In the majority of patients, ground glass opacities on chest radiographs progress rapidly to focal, multifocal or diffuse consolidation. Unilateral involvement is common in the early acute phase, becoming bilateral at maximal lung involvement. Generally, radiographic opacities peak between 8 and 10 days after onset of illness, with radiographic scores reflecting temporal changes in clinical and laboratory parameters such as oxygen saturation (SaO₂) and liver transaminases. Pleural effusions, cavitating consolidation and mediastinal lymphadenopathy are not typical radiographic features. Pneumomediastinum and pneumothoraces are complications that are associated with extensive disease, with or without assisted ventilation.
The utility of high resolution computed tomography (HRCT) and CT scans lies in the confirmation of airspace opacities in cases with normal initial chest radiographs that have strong contact history and signs and symptoms highly suspicious of SARS during the outbreak, allowing early treatment and prompt isolation. The characteristic HRCT feature in the acute phase is ground-glass opacities with smooth interlobular septal thickening, sometimes with consolidation in a subpleural location, which progress rapidly to involve other areas of the lungs. Temporal lung changes documented on HRCT suggest that some residual opacities found may not be reversible.     

Population changes in immunoglobulin-containing mononuclear cells in dextran sulfate sodium-induced coltitis

To investigate the relation of immunoglobulin-containing cells in the colonic mucosa to mucosal inflammation, we immunohistochemically examined the localization of immunoglobulin-containing mononuclear cells in the lamina propria in dextran sulfate sodium induced colitis in mice. Mice were treated repeatedly with 3% dextran sulfate sodium (MW 54 000) solution or distilled water for a total of 170 days (chronic model), or for 85 days (subacute model) or for 10 days (acute model). IgG, IgA, and IgM-containing mononuclear cells were studied by enzyme immunostaining. The number of IgA- and IgG-containing cells gradually and significantly increased in the acute, subacute, and chronic models, in that order (P<0.01 or 0.05). However, the numbers of IgM-containing cells in the three models were similar to that in the controls. These findings resembled those of human ulcerative colitis. In this dextran sulfate sodium-induced colitis, IgA-containing mononuclear cells may play an essential role in the mucosal immune system is the acute, subacute, and chronic phases. The finding that IgG-containing mononuclear cells increased substantially in the chronic phase suggests that IgG plays an important role in the mucosal inflammatory reaction during the chronic phase.     

Autoimmune Haemolytic Anaemia in Children

S ummary . Forty-four children with autoimmune haemolytic anaemia (AIHA) are described: 31 had acute, subacute or chronic disease with warm autoantibodies and 13 had acute or chronic anaemia with cold autoantibodies. The commonest forms were the acute and subacute types with warm autoantibodies and these were more frequent in young children, while chronic AIHA occurred mainly among children at puberty. In about 16% the anaemia was accompanied by a chronic disorder but in over 50% the anaemia was preceded by an acute infection or immunization. The former gave rise mainly to chronic anaemia, but the latter was associated with the acute and subacute forms. In general the prognosis was good and death was never caused by anaemia per se. The prognosis was worse in patients with clinical features of thrombocytopenia and bleeding and with the immunological findings of free autoantibodies in the serum and a positive direct antiglobulin test. In acute and subacute forms, treatment with corticosteroids and sometimes with blood transfusions was effective. In chronic forms of the disease it was often necessary to give additional immunosuppressive drugs or/and to perform a splenectomy.     

Radiologic findings in farmer's lung. Prognosis and correlation to lung function

We classified the radiologic findings of 93 patients with acute or subacute farmer's lung (FL) disease by type and severity of the change in chest x-ray film. Acute radiologic changes, further divided as nodular, ground-glass, or striated patchy opacities, were found in 78/93 patients at the first evaluation; 11 showed chronic changes (radiologic "fibrosis"), which persisted unchanged throughout the follow-up period; and four initially had a normal chest x-ray film. Patients were followed up 23 months on an average. The more severe the radiologic change at the first evaluation, the more impaired the diffusing capacity (Dsb). Severe radiologic changes disappeared more slowly than the less severe ones. The differences in the initial pulmonary function values between the two groups disappeared during the follow-up. The type of acute change did not predict the recovery of respiratory performance. Treatment with oral corticosteroids did not affect the outcome of lung function or appearance of chronic changes, although corticosteroids seemed to hasten the disappearance of diffuse opacities. At the final evaluation, the chest x-ray film was normal in 55/93 patients. Chronic changes were detected in 38 patients. Severe radiologic appearance and striated patchy opacities predisposed to development of chronic changes.     

Radiology of severe acute respiratory syndrome (SARS): the emerging pathologic-radiologic correlates of an emerging disease

Severe acute respiratory distress syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a systemic infection that clinically manifests as progressive pneumonia. During the initial phases of infection the virus causes pauci-inflammatory alveolar and interstitial edema that result in imaging abnormalities dominated by ground glass opacities (GGO). Severe SARS cases can develop radiologic and pathologic findings of diffuse alveolar damage. Although radiologic evidence of acute bronchiolitis is absent, SARS-CoV also infects ciliated airway epithelium, probably accounting for respiratory transmissibility of the virus. Radiologic recovery from SARS can be complete, but computed tomography images often show persistent GGO and reticular opacities, some of which reflect pathologic findings of fibrosis. Long-term follow-up imaging of survivors shows gradual decrease of GGO and reticulation with persistent air trapping in some patients. The latter is evidence of small airway disease that is not radiologically evident at the onset of the disease.     

Hypersensitivity pneumonitis

PURPOSE OF REVIEW: Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is a granulomatous, inflammatory disease of the lungs caused by the inhalation of antigenic organic particles or fumes. The disease may present as an acute, subacute, or chronic illness. Episodes of acute and subacute HP usually resolve following cessation of antigen exposure. Chronic HP may be progressive, irreversible, and result in debilitating fibrotic lung disease. This review discusses current concepts regarding the diagnosis, pathogenesis, and treatment of HP. RECENT FINDINGS: The pathogenesis of HP involves both type III and type IV hypersensitivity reactions that are mediated by immune complexes and Th1 T cells, respectively. Proinflammatory cytokines and chemokines activate alveolar macrophages, cause an influx of CD8+ lymphocytes into the lungs, facilitate granuloma formation, and promote the development of pulmonary fibrosis. IFN-gamma is essential for the development of HP and IL-10 appears to modulate the severity of disease. TNF-alpha and TGF-beta have been implicated in development of the pulmonary fibrosis that is seen in chronic HP. It has been shown that pigeon fanciers with HP have an increase in the frequency of HLA-DRB1*1305 and HLA-DQB1*0501 alleles, a decrease in the frequency of the HLA-BRB1*0802 allele, and an increased frequency of the TNF-2 (-308) polymorphism of the TNF-alpha promoter gene. SUMMARY: A careful environmental and occupational history and establishment of exposure to a known inciting antigen are key factors in making the diagnosis of HP. Serum precipitating antibodies, bronchoalveolar lavage, and lung biopsy may be helpful in making the diagnosis. Avoidance of organic antigen exposure is the most important factor in the management of HP. Corticosteroids are indicated for the treatment of severe acute and subacute HP and for chronic HP that is severe or progressive. Long-term corticosteroid therapy for the treatment of chronic HP should be considered only if objective improvement in clinical signs, pulmonary function, or radiographic abnormalities is documented.     

Sequential MRI studies of a patient with complex partial status--a case report

Complex partial status (CPS), the status epilepticus of complex partial seizure, is rarely seen in clinical practice. The clinical presentations of CPS are characterized by confusion, slowness in response, together with stereotypic or complex automatisms and occasional secondary generalization. The electroencephalographic findings of CPS reveal characteristic focal epileptiform activities of mesial temporal region. Magnetic resonance image (MRI) is the imaging method of choice for studying epilepsy, particularly when focus is in the temporal lobe. We report a 49-year-old female with diagnosis of viral encephalitis and clinical presentation of CPS. We present the sequential brain MRI findings at acute, subacute and chronic stages of this patient.     

The evolution of experimental Trypanosoma cruzi cardiomyopathy in rabbits: further parasitological, morphological and functional studies

Young rabbits (1–2 months of age) inoculated with trypomastigote forms of the Colombia strain of Trypanosoma cruzi have been shown to develop cardiac pathological changes (together with parasitological and immunological alterations) which are very similar to those observed in the acute and chronic phases of Chagas' disease in man. The cardiac alterations in the acute phase are characterized grossly by slight cardiomegaly with dilatation of the right-sided chambers. Microscopically they are characterized by mild focal myocarditis. The chronic phase is characterized by moderate to marked cardiomegaly with hypertrophy and dilatation of both ventricular chambers. There is thinning of the apical region (apical aneurysm), particularly of the left ventricle. Focal myocarditis is seen microscopically with areas of myocytolytic necrosis, atrophic and hypertrophic myofibers, an inflammatory response predominantly composed of mononuclear cells and interstitial fibrosis. Cineventriculography in the left ventricle of rabbits during the chronic phase disclosed regional myocardial dysfunction, with typical apical systolic bulging. The pathogenesis of Chagasic cardiomyopathy is briefly discussed in the light of these findings. Our investigation has further shown that this animal model is particularly suitable for studies on the mechanisms, pathology and treatment of Chagas' heart disease.     

Leflunomide-related lung injury in patients with rheumatoid arthritis: imaging features

Imaging findings of 26 cases of leflunomide (Arava)-related acute lung injury were analyzed. Thirteen cases had pre-existing interstitial pulmonary disease on chest X-ray or computed tomography. The main features of clinically determined leflunomide-induced acute lung injury were similar to those caused by other drugs: diffuse or widespread patchy ground-glass opacities and/or consolidation, frequently accompanied by septal thickening and intralobular reticular opacities. We categorized these findings into four patterns: diffuse alveolar damage (DAD), acute eosinophilic pneumonia, hyperreaction, and cryptogenic organizing pneumonia. The DAD group had a higher mortality rate, but statistically not a significant one. It is impossible to exclude infectious disease such as pneumocystis carinii pneumonia based on imaging findings, and detailed correlation of imaging findings with clinical and laboratory findings is essential in order to make a correct diagnosis.     

Large-scale disaster and gastrointestinal diseases

Many medical investigations, including epidemiological studies, case reports and case series have been conducted in association with large-scale disasters worldwide. Gastrointestinal diseases have been identified in many studies on disaster-related diseases with various problems being encountered especially in the acute (the first 3 days after the onset of a disaster), subacute (approximately the first 2 weeks after the onset of a disaster), and chronic phases. The problems in the acute phase concern food security and nutrition, while those in the subacute phase concern constipation and diarrhea. According to each disease site, the clinically important problems in the chronic phase are peptic ulcer and functional dyspepsia affecting the upper gastrointestinal tract, and inflammatory bowel disease and irritable bowel syndrome affecting the lower gastrointestinal tract. In addition, chronic hepatitis B and alcoholic liver diseases/pancreatitis are major hepatobiliary pancreatic diseases.     

Acute interstitial pneumonia: diagnostic approach and management

Acute interstitial pneumonia (AIP) encompasses a spectrum of pulmonary disorders characterized by involvement of the lung interstitium and distal airways (bronchioles and alveoli). The onset of respiratory symptoms is acute, most often within two weeks. Most AIP take place de novo, but sometimes represent an acute exacerbation of chronic lung disease. The clinical presentation of AIP comprises rapidly progressive dyspnoea, associated sometimes with cough, fever, myalgia and asthenia. Chest radiography shows diffuse pulmonary opacities. The associated hypoxemia may be severe enough to cause acute respiratory failure. Underlying aetiologies are numerous and variable, particularly in relation to the underlying immune status of the host. Various histopathological entities may be responsible for AIP although diffuse alveolar damage is the predominant pattern. The diagnostic approach to a patient presenting with AIP is to try to determine the most likely underlying histopathological pattern and to search for a precise aetiology. It relies mainly on a meticulous clinical evaluation and accurate biological investigation, essentially guided by the results of bronchoalveolar lavage performed in an area identified by abnormalities on high resolution computed tomography of the lungs. Initial therapeutic management includes symptomatic measures, broad-spectrum antibiotic treatment adapted to the clinical context, frequently combined with systemic corticosteroid therapy.     

An experimental model for myocarditis and congestive heart failure after rabbit coronavirus infection.

In a model for virus-induced myocarditis and congestive heart failure, rabbit coronavirus infection was divided into acute (days 2-5) and subacute (days 6-12) phases on the basis of day of death and pathologic findings. During the acute phase, the principal histologic lesions were degeneration and necrosis of myocytes, myocytolysis, interstitial edema, and hemorrhage. The severity of these changes increased in the subacute phase. Pleural effusion and congestion of the lungs and liver were also present at this time. Myocarditis was detected by day 9 and peaked by day 12. Heart weights and heart weight-to-body weight ratios were increased, and dilation of the right ventricular cavity became prominent early in infection and persisted. In contrast, dilation of the left ventricle occurred late in the subacute stage. Virus was isolated from infected hearts between days 2 and 12. These data suggest that rabbit coronavirus infection progresses to myocarditis and congestive heart failure.     

A case of subacute idiopathic interstitial pneumonia resistant to steroids, successfully treated with cyclophosphamide]

A 47-year-old woman was admitted to our hospital because of dry cough, fever, and subacute, progressive dyspnea. Chest radiography and computed tomography showed ground glass opacities in the lower lung fields. We suspected pneumonia caused by atypical pathogens and administered antibiotics, but they had no effect at all. Histopathologic findings from a transbronchial lung biopsy (TBLB) included intensive infiltration of mononuclear cells and edema on the alveolar wall with no evidence of fibrosis, fibroblasts, hyaline membrane, or granuloma. On the basis of these findings, we suspected interstitial pneumonia, but a surgical lung biopsy was not possible because the patient would not give her consent. After TBLB, corticosteroid was administered repetitively, but dyspnea was deteriorating as the ground glass opacities became more widespread, and tractional bronchiectasis appeared throughout the lung fields. Therefore, we decided to administer cyclophosphamide (CPA). This was very effective: all of her symptoms improved and the ground glass opacities and tractional bronchiectasis disappeared. Though we tapered and then discontinued corticosteroids a few months after CPA, there was no recurrence whatever. No signs suggesting the association of collagen vascular diseases were detected. The effectiveness of CPA in interstitial pneumonia associated with collagen vascular disease is occasionally reported, but the effect on idiopathic interstitial pneumonia, especially in acute and subacute progressive cases, is rarely reported. We think this is an interesting case to consider the availability of CPA in idiopathic interstitial pneumonia with subacute progression.     

Biochemical characteristics of fluid and cells of bronchoalveolar washings in patients with extrinsic allergic alveolitis

In 43 patients with exogenous allergic alveolitis (EAA), including 30 and 13 in its acute and chronic disease, bronchoalveolar lavage was performed, bronchoalveolar washing fluid (BAWF), isolated alveolar macrophages (AM) and unfractionated cellular sediment (NFCS) were separately studied. The BAWF showed high rates of lipid peroxidation (LPO), decreased antiproteolytic defense, and activated local synthesis of haptoglobin (Hp), fibronectin (FN), platelet activation factor (PAF), and enzymes of antioxidative defense (AOD). There was a rise in FN and PAF concentrations in the acute phase of the disease and higher PLO rates and elevated Hp levels in chronic EAA. The rate of oxidative metabolism in AMs was much higher in acute EAA than that in chronic EAA and accompanied by imbalance in the PLO-AOD system. AM levels of PAF was high in patients in both groups. The rate of LPO was higher in NFCS than in AM and was also followed by simultaneous AOD mobilization with preserved imbalance. A particularly significant AOD insufficiency in the NFCS was noted in chronic EAA, which was accompanied by decreased PAF. Thus, local pathochemical processes are of significance in developing the pattern of the process in EAA.     

Cavographic study of an early stage of obstruction of the hepatic portion of the inferior vena cava

BACKGROUND: Liver disease caused by a chronic lesion of the hepatic portion of the inferior vena cava (IVC) is clinically characterized by dilated superficial veins in the body trunk with cephalad flow, hepatomegaly and splenomegaly. Cavography shows stenosis or complete obstruction near the cava-atrial junction. METHODS: Early (acute and subacute) forms of the disease were recognized. The early stage of the disease manifested as jaundice, hepatomegaly or ascites and fever. Patients with acute and subacute onset of the illness with no past history of liver disease were studied with inferior vena cavography. Some of the patients had repeat cavography at 6 months and at 1 year after the initial investigations. RESULTS: Three types of cavographic lesions were observed in the early stages of the disease: type 1, linear lucent area in the IVC close to cava-atrial junction; type 2, a smooth or irregular narrowing of almost the whole segment of the hepatic portion of the IVC; and type 3, a constriction or narrowing of a segment of the IVC near the cava-atrial junction. The first two types were associated with the acute stage of the disease and type 3 with the subacute stage. Type 2 and 3 lesions were associated with post-stenotic dilatation (PSD) close to the atrium. Lucent areas resulting from thrombosis are common in PSD. The acute and subacute hepatic IVC diseases in Nepal are commonly associated with bacterial infection. CONCLUSIONS: It is postulated that the early cavographic lesions are consistent with thrombosis and thrombophlebitis of the hepatic portion of the IVC, and that resolution of the lesions leads to the development of stenosis and to complete obstruction.     

外源性变应性肺泡炎的临床病理特征和影像学表现

目的探讨外源性变应性肺泡炎(EAA)的临床病理特征和影像学表现。方法分析5例外源性变应性肺泡炎病例的临床特点、影像学表现、肺活检的病理特征。结果 EAA常见的临床表现为咳嗽、呼吸困难、咳痰、发热;主要阳性体征为轻度紫绀、肺部听诊湿啰音或Velcro啰音;肺功能检查显示限制性通气功能障碍和弥散功能障碍。HRCT表现为磨玻璃影、小叶间隔增厚、小叶中心性结节、网格影和蜂窝肺等。支气管肺泡灌洗液显示淋巴细胞增多。肺活检组织病理学示淋巴细胞性间质性肺炎,细支气管周围可见小的不典型肉芽肿和多核巨细胞。患者对糖皮质激素治疗有效。结论临床表现结合影像学特点可提示EAA临床诊断,肺活检是诊断EAA有效的检查方法。