Intractable diffuse pulmonary diseases: Manual for diagnosis and treatment.

This manual has been compiled by a joint production committee with the Diffuse Lung Disease Assembly of the Japanese Respiratory Society (JRS) to provide a practical manual for the epidemiology, diagnosis, and treatment of intractable diffuse pulmonary diseases. The contents are based upon the results of research into these diseases by the Diffuse Pulmonary Diseases Study Group (principal researcher: Sakae Homma) supported by the FY2014-FY2016 Health and Labor Sciences Research Grant on Intractable Diseases. This manual focuses on: 1) pulmonary alveolar microlithiasis, 2) bronchiolitis obliterans, and 3) Hermansky-Pudlak Syndrome with interstitial pneumonia. As these are rare/intractable diffuse lung diseases (2 and 3 were first recognized as specified intractable diseases in 2015), there have not been sufficient epidemiological studies made, and there has been little progress in formulating diagnostic criteria and severity scales; however, the results of Japan's first surveys and research into such details are presented herein. In addition, the manual provides treatment guidance and actual cases for each disease, aiming to assist in the establishment of future modalities. The manual was produced with the goal of enabling clinicians specialized in respiratory apparatus to handle these diseases in clinical settings and of further advancing future research and treatment.

Sarcoidosis in the aged: review and management.

PURPOSE OF REVIEW: We intend to update the data of various clinical features and management of sarcoidosis in the aged. RECENT FINDINGS: Subclinical or inapparent systemic involvement of sarcoidosis was found at autopsy in elderly patients who died from sarcoidosis, complication of malignancy, or cerebrovascular accidents. Sarcoidosis in the aged presents with unusual intrathoracic and extrapulmonary clinical features. Occasionally, these features may masquerade as malignancy. Sarcoidosis may appear or reactivate in patients receiving treatment with tumor necrosis factor antagonists or antiviral treatment. In elderly patients, antitumour necrosis factor treatment is effective for refractory sarcoidosis, methylphenidate hydrochloride for fatigue, and bosentan for sarcoidosis-associated pulmonary hypertension. Inhaled prostacyclin has been found to be effective in some patients with pulmonary hypertension. Sarcoidosis and malignancy can coexist. SUMMARY: Autopsy studies revealed that both apparent and subclinical or inapparent systemic involvement of sarcoidosis might exist in aged patients with sarcoidosis. Aged sarcoidosis patients often present with unusual clinical features of sarcoidosis. Occasionally, these features resemble malignancy. New treatment with tumor necrosis factor antagonists for intractable sarcoidosis, methylphenidate hydrochloride for fatigue, and bosentan for sarcoidosis-associated pulmonary hypertension may be effective in sarcoidosis in the aged. Sarcoidosis and malignancy may coexist.

Pulmonary alveolar microlithiasis: review and management.

PURPOSE OF REVIEW: Our knowledge of pulmonary alveolar microlithiasis (PAM) has significantly increased since its detailed description by Sosman in 1957. Here we provide updated information on the long-term clinical course, the specific findings in imaging studies and the genetics of this disease. RECENT FINDINGS: The responsible gene, the mutation of which is associated with PAM, has been identified as SLC34A2. Characteristic chest computed tomography (CT) findings in patients with PAM have been shown to correlate well with specific pathological findings. Elevated serum levels of surfactant proteins A and D have also been reported in this disease. Long-term follow up information has been updated. SUMMARY: The gene responsible for PAM, SLC34A2, has been identified. It encodes a type IIb sodium-dependent phosphate transporter, the function of which provides an insight into the pathogenesis of this disease. The demonstration of a mutation in the SLC34A2 gene helps to confirm the diagnosis of PAM. Characteristic chest CT findings that include irregular thickening of perilobular interstitium and calcification along perilobular structures correlate with specific pathological findings. Serum levels of surfactant proteins A and D correlate with the progression of the disease, and may be a useful monitoring tool. Scrutiny of the long-term follow-up data of PAM patients reveals that the prognosis for PAM is poor. The establishment of an effective treatment, which is not yet available, is mandatory.

Mutations in the SLC34A2 gene are associated with pulmonary alveolar microlithiasis.

RATIONALE: Pulmonary alveolar microlithiasis is an autosomal recessive disorder in which microliths are formed in the alveolar space. OBJECTIVES: To identify the responsible gene that causes pulmonary alveolar microlithiasis. METHODS: By means of a genomewide single-nucleotide polymorphism analysis using DNA from three patients, we have narrowed the region in which the candidate gene is located. From this region, we have identified a gene that has mutations in all patients with pulmonary alveolar microlithiasis. MEASUREMENTS AND MAIN RESULTS: We identified a candidate gene, SLC34A2, that encodes a type IIb sodium phosphate cotransporter and that is mutated in six of six patients investigated. SLC34A2 is specifically expressed in type II alveolar cells, and the mutations abolished the normal gene function. CONCLUSION: Mutations in the SLC34A2 gene that abolish normal gene function cause pulmonary alveolar microlithiasis.

Elevated serum surfactant protein A and D in pulmonary alveolar microlithiasis.

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterized by widespread localization of calcispherites in the alveolar spaces. The authors report two cases of PAM, with markedly elevated sera concentrations of surfactant protein-A and surfactant protein-D, which showed a tendency to increase as the disease progressed. Therefore, surfactant protein-A and surfactant protein-D may function as serum markers to monitor the disease activity and progression of PAM.

Prevention of left ventricular remodeling by long-term corticosteroid therapy in patients with cardiac sarcoidosis.

Forty-three patients with cardiac sarcoidosis were studied echocardiographically before and after (mean follow-up 88 months) steroid therapy to determine the effectiveness of corticosteroids to prevent left ventricular (LV) remodeling and improve LV contractility. In patients with initial LV ejection fractions (LVEFs) >or=55%, long-term steroid therapy showed preventive effects for LV remodeling and LV function. Patients with LVEF <54% showed significant reductions of LV volumes and LVEF improvement. However, in patients with LVEFs <30%, steroid therapy resulted in neither LV volume reductions nor improved LVEFs. In the early or middle stage of the disease, steroid therapy may be protective or therapeutic in preventing LV remodeling and preserving LV function. However, it may not be as effective in the late stage.

Clinical characteristics of 195 Japanese sarcoidosis patients treated with oral corticosteroids.

Questionnaires were sent to 46 hospitals of all over Japan in order to obtain the clinical data on sarcoidosis patients who were treated with oral corticosteroids. The number of female patients was greater than that of male patients (1.5:1), and the average age was 44.9 +/- 16.5 with peaks at 20 and at 50 to 60. The markers of disease activity were high in serum or bronchoalveolar lavage fluids (BALF): specifically, the serum angiotensin-converting enzyme (sACE) was 27.9 +/- 31.9 IU/ml (n.v. < 21.4), and the CD4/CD8 lymphocyte ratio was 6.5 +/- 5.7. Eye involvement was the most common reason for systemic steroid therapy, followed in order by lung and heart involvement. The main reasons for steroid therapy were the exacerbation of ocular symptoms, visual disturbance, respiratory symptoms, such as cough or exertional dyspnea, progression of chest radiographic findings, heart failure and severe arrhythmia, such as AV block. The initial corticosteroid dose was usually 30 mg of predinisolone per day, but for some refractory cases, a 40-60 mg per day was used. Immunosuppressive drugs, such as methotrexate, were also used in the small number of patients who responded poorly to the steroid. Overall, a good clinical response to the drug was found in 70-80% of the steroid treated patients, but in those with cardiac disease, the response rate was only 48%.