BACKGROUND: Although many risk factors are known to be associated with poor asthma outcomes in the elderly, the literature on the effect of risk factor control on asthma outcomes in the elderly is very sparse. OBJECTIVE: To evaluate the role of multifaceted interventions in reducing acute exacerbations in elderly asthmatics. METHODS: A total of 100 subjects were randomly selected from our prospective cohort of elderly asthmatics aged 65 years or older and were provided multifaceted intervention for 1 year. Our multifaceted interventions included repeated education on asthma and inhaler technique for patients and their caregivers, provision of an action plan to cope with acute exacerbations, short message service to prevent follow-up losses, and oral replacement of magnesium. The primary outcome was an acute asthma exacerbation rate compared to the previous year. RESULTS: Ninety-two subjects completed this study, although only 58 subjects continued to take magnesium. Compared to the previous year, the acute asthma exacerbation rate showed a significant reduction from 67% to 50% (p = 0001) and significant improvement was observed in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) (p = 0.04, p = 0.036 for each). Interestingly, a subgroup analysis revealed that predicted value of FEV1 increased significantly in subjects who continued to take magnesium from 79.6% to 87.1% (p = 0.008). CONCLUSION: To reduce acute exacerbations in elderly asthmatics, a multifaceted approach in increase medical awareness, proficiency and adherence to inhaler, assistance of caregivers and correction of micronutrients deficiency is likely to be effective. In addition, a continuous oral replacement of magnesium may increase FEV1 in elderly asthmatics.
Aged ; Asthma ; Caregivers ; Cohort Studies ; Education ; Follow-Up Studies ; Forced Expiratory Volume ; Humans ; Magnesium ; Micronutrients ; Nebulizers and Vaporizers ; Prospective Studies ; Risk Factors ; Text Messaging ; Vital Capacity

PURPOSE: The prevalence of asthma in the elderly is rapidly increasing. However, we do not fully understand the pathogenesis of elderly asthma, especially for the roles of micronutrients. This study aimed to evaluate the associations between serum levels of micronutrients, including several vitamins and minerals, and clinical features of the elderly asthmatics. METHODS: A total of 317 asthmatics aged 65 or older were enrolled. Serum levels of vitamin D, vitamin B₁₂, folate, Mg, and Se were measured and then the associations between serum micronutrient levels and clinical features of elderly asthmatics were evaluated. RESULTS: Positive correlations with significance among serum levels of vitamin B₁₂, vitamin D, and folate were found. Serum micronutrients levels showed no difference according to the atopic status and symptom severity. The serum folate level was significantly associated with forced expiratory volume in 1 second, and serum vitamin B₁₂ and folate levels were significantly associated with serum total IgE level. Interestingly, elderly asthmatics with exacerbation history showed significantly lower serum levels of vitamin D and Mg, but significantly higher serum levels of Se. CONCLUSION: Serum levels of micronutrients, such as vitamin D, vitamin B₁₂, Mg, folate, and Se, were significantly associated with some clinical features of elderly asthmatics. Clinical meanings of these associations need to be investigated further.
Aged* ; Asthma ; Folic Acid ; Forced Expiratory Volume ; Humans ; Immunoglobulin E ; Micronutrients* ; Minerals ; Miners ; Prevalence ; Vitamin D ; Vitamins

PURPOSE: Endoplasmic reticulum (ER) stress has recently been observed to activate NF-kappaB and induce inflammatory responses such as asthma. Activating transcription factor 6beta (ATF6B) is known to regulate ATFalpha-mediated ER stress response. The aim of this study is to investigate the associations of ATF6B genetic variants with aspirin-exacerbated respiratory disease (AERD) and its major phenotype, % decline of FEV1 by aspirin provocation. METHODS: Four common single nucleotide polymorphisms (SNPs) of ATF6B were genotyped and statistically analyzed in 93 AERD patients and 96 aspirin-tolerant asthma (ATA) as controls. RESULTS: Logistic analysis revealed that 2 SNPs (rs2228628 and rs8111, P=0.008; corrected P=0.03) and 1 haplotype (ATF6B-ht4, P=0.005; corrected P=0.02) were significantly associated with % decline of FEV1 by aspirin provocation, whereas ATF6B polymorphisms and haplotypes were not associated with the risk of AERD. CONCLUSIONS: Although further functional and replication studies are needed, our preliminary findings suggest that ATF6B may be related to obstructive phenotypes in response to aspirin exposure in adult asthmatics.
Adult ; Aspirin* ; Asthma ; Endoplasmic Reticulum ; Haplotypes ; Humans ; Methods ; NF-kappa B ; Phenotype ; Polymorphism, Single Nucleotide ; Transcription Factors

PURPOSE: Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1). METHODS: A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls. RESULTS: This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (P corr>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (P corr>0.05). CONCLUSIONS: Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD.
Aspirin ; Asthma ; Contractile Proteins ; Eating ; Forced Expiratory Volume ; Haplotypes ; Humans ; Hypersensitivity ; Membranes ; Microfilament Proteins ; Negotiating ; Polymorphism, Single Nucleotide

A 70-yr-old woman visited our hospital for shortness of breath. Chest CT showed ground glass opacity and traction bronchiectasis at right middle, lower lobe and left lingular division. Video-assisted thoracic surgical biopsy at right lower lobe and pathologic examination revealed mixed dust pneumoconiosis. Polarized optical microscopy showed lung lesions were consisted of silica and carbon materials. She was a housewife and never been exposed to silica dusts occupationally. She has taken freshwater snails as a health-promoting food for 40 yr and ground shell powder was piled up on her backyard where she spent day-time. Energy dispersive X-ray spectroscopy of snail shell and scanning electron microscopy with energy dispersive x-ray spectroscopy of lung lesion revealed that silica occupies important portion. Herein, we report the first known case of silicosis due to chronic inhalation of shell powder of freshwater snail.
Aged ; Animals ; Carbon/chemistry ; *Dust ; Female ; Humans ; *Inhalation ; Silicon Dioxide/chemistry ; Silicosis/*diagnosis/radiography ; Snails/*chemistry ; Spectrometry, X-Ray Emission ; Tomography, X-Ray Computed

An eighteen year-old female visited the ER in our hospital with fever of 38.5degrees C for 2 days. She also had cough, myalgia, and dyspnea. Chest PA and lung HRCT showed mild pulmonary edema at both hilar areas. However, she had severe hypoxia (PaO2; 58 mmHg in room air). RT-PCR for H1N1 influenza/A of pharyngeal swab was positive. Tamiflu (150 mg/d) with broad-spectrum antibiotics was prescribed. Two days later, her dyspnea aggravated and chest PA showed diffuse bilateral infiltration. PaO2 dropped to 70 mmHg (O2 10 L/min by face mask with reservoir bag). She was transferred to the MICU and the Tamiflu dose was doubled (300 mg/day). Mechanical ventilator was set aside to prepare respiratory failure. Fortunately, her symptoms and oxygenation improved and she was discharged with full recovery. Although, most cases of ARDS require mechanical ventilatory support, early and adequate dose of Tamiflu may avoid it in the case of ARDS developed by H1N1 influenza/A.
Anoxia ; Anti-Bacterial Agents ; Cough ; Dyspnea ; Female ; Fever ; Humans ; Lung ; Masks ; Oseltamivir ; Oxygen ; Pneumonia ; Pulmonary Edema ; Respiratory Insufficiency ; Thorax ; Ventilators, Mechanical

BACKGROUND: Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea, and has shown antiproliferative, antiangiogenic, antimetastatic and cell cycle pertubation activity in various tumor models. Hypoxia can be induced because angiogenesis is insufficient for highly proliferating cancer. Hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream target, vascular endothelial growth factor (VEGF), are important for angiogenesis, tumor growth and metastasis. The aim of this study was to determine how hypoxia could cause changes in the cellular phenomena and microenvironment in a non-small cell culture system and to examine the effects of EGCG on a HIF-1alpha and VEGF in A549 cell line. METHODS: A549 cells, a non-small cell lung cancer cell line, were cultured with DMEM and 10% fetal bovine serum. A decrease in oxygen tension was induced using a hypoxia microchamber and a CO2-N2 gas mixture. Gas analysis and a MTT assay were performed. The A549 cells were treated with EGCG (0, 12.5, 25, 50 micromol/L), and then examined by real-time-PCR analysis of HIF-1alpha, VEGF, and beta-actin mRNA. RESULTS: Hypoxia reduced the proliferation of A549 cells from normoxic conditions. EGCG inhibited HIF-1alpha transcription in A549 cells in a dose-dependent manner. Compared to HIF-1alpha, VEGF was not inhibited by EGCG. CONCLUSION: HIF-1alpha can be inhibited by EGCG. This suggests that targeting HIF-1alpha with a EGCG treatment may have therapeutic potential in non-small cell lung cancers.
Actins ; Anoxia ; Carcinoma, Non-Small-Cell Lung ; Catechin ; Cell Culture Techniques ; Cell Cycle ; Cell Line ; Humans ; Lung ; Lung Neoplasms ; Neoplasm Metastasis ; Oxygen ; RNA, Messenger ; Tea ; Vascular Endothelial Growth Factor A

Idiopathic hypereosinophilic syndrome is characterized by multiorgan involvement without any cause, and peripheral eosinophilia(1,500/microliter) for more than 6 months. Clinically, many organs can be involved, but the heart is the most commonly involved organ. Although lung involvement is usual(20-30%)1) in hypereosinophilic syndrome, there are few reports of eosinophilic pneumonia proven by biopsy confirmation in Korea. We experienced a case of hypereosinophilic syndrome with eosinophilic pneumonia and bronchitis confirmed by biopsy, and we report it here with a review of the literature.
Biopsy ; Bronchitis* ; Eosinophils* ; Heart ; Hypereosinophilic Syndrome* ; Korea ; Lung ; Pulmonary Eosinophilia*

BACKGROUND: To evaluate airway responses and inflammation to antigen in Sprague-Dawley rat asthma model, we examined airway responses, serial histologic changes of the lung, and the relationship between airway responses and airway inflammation after antigen airway challenge. METHODS: Sprague-Dawley rats were sensitized with subcutaneous injection of 10 microgram ovalbumin(OA). Antigen airway challenges were done 14 ~16 days after sensitization and the sensitized rats were sacrificed 1h(AE), 6 ~8h(AL) and 1day(AD) after airway challenge, to examine the histologic changes of the lung. Airway responses were measured by body plethysmograph and recorded by enhanced pause(Penh) as an index of airway obstruction 6 ~8h after antigen challenges. Nonsensitized controls(10 rats) were also challenged with antigen and sacrificed 1 day later. Histopathologic examination of two trachea, large bronchi, small bronchi, and vessels was performed to evaluate the severity of inflammation and eosinophilic infiltration with H&E stain. RESULTS: In 17 of 20 rats(85%) in both groups, we observed airway responses. Among them, an early response(ER) in 15 rats(75%), an dual response in 5(25%), and an late response(LR) only in 2 rats(10%) displayed. There were no significant differences in the severity of inflammation among the trachea, large bronchi, small bronchi and vessels in all groups after antigen challenge(p>0.05) and between early and late responders. The significant eosinophil infiltration was observed in 5 rats(50%) of AL(p<0.05) compared with in AE and controls. Also, eosinophil infiltration was observed in higher trend in LR(57.1%) compared to ER(40%)(p>0.05). CONCLUSION: Sprague-Dawley rats sensitized with subcutaneous injection of OA showed a significant airway responses to antigen challenge. But antigen challenges caused a little eosinophil infiltration and no significant airway inflammation. Asthma model of Sprague-Dawley rats could be useful for antigen-induced airway responses, but this model has a limitation for the study of human asthma because of no significant pathologic change.
Airway Obstruction ; Animals ; Asthma* ; Bronchi ; Eosinophils ; Humans ; Inflammation* ; Injections, Subcutaneous ; Lung ; Ovalbumin* ; Rats ; Rats, Sprague-Dawley* ; Trachea

BACKGROUND: Acute lung injury is an hypoxic respiratory failure resulting from damage to the alveolar-capillary membrane, which can be developed by a variety of systemic inflammatory diseases. In this study the therapeutic effects of intra-tracheal pulmonary surfactant instillation was evaluated in the intratracheal endotoxin induced acute lung injury model of a rat. METHODS: 20 Twenty Sprague-Dawley rats were divided into 4 groups, and normal saline (2 ml/kg, for group 1) or LPS (5 mg/kg, for group 2, 3, and 4) was instilled into the trachea respectively. Either normal saline (2 ml/kg, for group 1 & 2, 30 min later) or bovine surfactant (15 mg/kg, 30 min later for group 3, 5 hr later for group 5) was instilled into the trachea. The therapeutic effect of intratracheal surfactant therapy was evaluated with one chamber body plethysmography (respiratory frequency, tidal volume and enhanced pause), ABGA, BAL fluid analysis (cell count with differential, protein concentration) and pathologic examination of the lung. RESULTS: Intratracheal endotoxin instillation induced increase in increased the respiration rate, decrease in decreased the tidal volume and increase in increased the Penh in all group of rats. Intratracehal instillation of surfactant decreased Penh, increased arterial oxygen tension, decreased protein concentration of BAL fluid and decreased lung inflammation in at both time times of administration (30 minute and 5 hour after endotoxin instillation). CONCLUSION: Intratracheal instillation of surfactant would be can be a beneficial therapeutic modality as discovered in the acute lung injury model of rats induced by intratracheal LPS intillation. It deserves to be evaluated in the fortreatment of human acute lung injury.
Acute Lung Injury* ; Animals ; Humans ; Lung* ; Membranes ; Oxygen ; Plethysmography ; Pneumonia ; Pulmonary Surfactants ; Rats* ; Rats, Sprague-Dawley ; Respiratory Insufficiency ; Respiratory Rate ; Tidal Volume ; Trachea