Yuki Sumi

Clinical features of recurrent and insidious chronic bird fancier's lung

BACKGROUND Chronic bird fanciers lung (BFL) can be subgrouped into two types. One subgroup of patients develops interstitial pulmonary fibrosis after recurrent acute episodes (recurrent BFL), and the other subgroup of patients has no history of acute episodes but has slowly progressive chronic respiratory disease (insidious BFL). OBJECTIVE To define the clinical characteristics of both types of BFL and to provide clues for diagnosis. METHODS We performed a retrospective review of the medical records of patients with chronic BFL who were evaluated between October 1992 and March 2001 at the Tokyo Medical and Dental University Hospital in Japan. Patients were evaluated for their clinical characteristics, including history, laboratory, and immunologic findings; imaging; bronchoalveolar lavage; and histologic findings. RESULTS Thirty-two patients with chronic BFL were included in this study; 15 patients had recurrent BFL and 17 had insidious BFL. The patients with recurrent BFL tended to breed dozens of pigeons in a loft, whereas the patients with insidious BFL were likely to be exposed to smaller birds kept indoors. Specific antibodies against pigeon dropping extracts or budgerigar dropping extracts were positive in 87% of the recurrent BFL cases and 35% of the insidious BFL cases. Antigen-induced lymphocyte proliferation was positive in more than 90% of both groups. The upper lung field was frequently involved in both groups as demonstrated by chest radiographic findings. In all of the patients with insidious BFL, the diagnosis was confirmed by positive laboratory-controlled inhalation test results. CONCLUSIONS Insidious BFL may be misdiagnosed as idiopathic pulmonary fibrosis if a careful history is not taken and antigen-induced lymphocyte proliferation, careful imaging evaluation, and laboratory-controlled inhalation challenge testing are not conducted. In contrast, the clinical findings of recurrent BFL are consistent with hypersensitivity pneumonitis induced by other antigens.

A follow-up study of pulmonary function tests, bronchoalveolar lavage cells, and humoral and cellular immunity in bird fancier's lung

BACKGROUND AND OBJECTIVE The long-term outcome of bird fanciers lung appears to be variable. The objective of this study is to clarify the sequelae of disease process in bird fanciers lung, with special reference to the humoral and cellular immune responses after avoidance of direct antigen exposure. METHODS Five patients with bird fanciers lung were studied for various parameters including pulmonary function tests, cellular profiles of bronchoalveolar lavage (BAL) fluids, determinations of antibodies in BAL fluids and sera, and antigen-induced proliferation of peripheral and bronchoalveolar lymphocytes during the 5 years of follow-up. RESULTS Four of five patients showed improvement in pulmonary function, and one showed marked deterioration. This patients room was close to the pigeon coop where her son was breeding pigeons, resulting in low-grade antigenic stimulation. Three patients demonstrated an increase in CD8+ cells in BAL fluid, but the remaining two showed an increase in CD4+ cells. The levels of IgA antibodies remained unchanged, whereas IgG levels started declining after the first 3 years of follow-up. Antigen-induced proliferation of BAL lymphocytes from all five patients and blood lymphocytes from four of five patients became weaker and gradually approached normal levels. One patient had pulmonary fibrosis and showed significant reduction in pulmonary functions but elevated reactivity of BAL lymphocytes to pigeon antigens. CONCLUSION This follow-up study demonstrates persistence of sensitized lymphocytes and antibody production in the respiratory tract and warrants careful evaluation of patients with bird fanciers lung, even after antigen avoidance.

A clinical study of hypersensitivity pneumonitis presumably caused by feather duvets

BACKGROUND Bird fanciers lung (BFL) is a type of hypersensitivity pneumonitis induced by the inhalation of bird-related antigens. The BFL induced by feathers is difficult to diagnose because feathers are generally unrecognized as a causative antigen. OBJECTIVE To determine the clinical features of BFL presumably induced by feather duvets (feather duvet lung) to provide clues for diagnosis. METHODS We performed a retrospective review of the medical records of patients with feather duvet lung evaluated between April 1, 2000, and June 30, 2003, at the Tokyo Medical and Dental University Hospital in Japan. RESULTS Seven patients with feather duvet lung were included in this study; 4 patients had acute disease and 3 had chronic BFL. Duration of contact with feather duvets was 1 month to 10 years. Serum KL-6 and surfactant protein D levels were elevated in all the patients. Specific antibodies against avian antigens were positive in acute BFL but negative in chronic BFL. Antigen-induced lymphocyte proliferation in peripheral blood or bronchoalveolar lavage cells was positive in all the patients. The diagnosis was confirmed by an environmental or inhalation provocation test. CONCLUSIONS Feather duvets can induce acute and chronic BFL. Physicians should be aware of feather duvets as a cause of BFL because feather duvets are becoming more prevalent.

Purification of the antigenic components of pigeon dropping extract, the responsible agent for cellular immunity in pigeon breeder's disease

BACKGROUND Pigeon breeders disease (PBD) is a lung disease caused by inhalation of antigens derived from pigeons. OBJECTIVE This study was undertaken to characterize the responsible component of pigeon dropping extract (PDE) for PBD. METHODS First, crude PDE was applied to SDS-PAGE followed by immunoblotting by using antibodies in bronchoalveolar lavage (BAL) fluid. Second, 9 bands of PDE were separated by SDS-PAGE and used for antigen-induced PBMCs. Finally, amino-terminal sequencing was conducted on an isolated 21-kd protein by 2-dimensional electrophoresis. RESULTS Immunoblots with BAL fluid from patients with PBD identified 9 bands. Similar patterns were observed by using BAL fluid from 10 control patients (9 with summer-type hypersensitivity pneumonitis or idiopathic pulmonary fibrosis and 1 asymptomatic breeder), except for the 21-kd protein, which was detected in 10 patients with PBD and 1 asymptomatic breeder. The stimulation indices of PBMCs determined by using proteins electroeluted from the 9 bands were higher in patients with PBD than in the 10 control patients. The 21-kd protein was separated into 5 spots by 2-dimensional electrophoresis; these spots were all reactive with BAL fluid from patients with PBD as determined by immunoblotting. The sequence of the 21-kd protein had 57% identity to a Saccharomyces cerevisiae chromosome X reading frame. A synthetic peptide, derived from the amino acid sequence of the N-terminal of the native protein, induced significant proliferation of PBMCs obtained from 5 patients with PBD, but not with PBMCs obtained from control patients. CONCLUSION The 21-kd protein is the only protein that identified individuals exposed to pigeons by immunoblotting. Only PBMCs from patients with PBD showed significant proliferation to the 21-kd protein and to the synthetic peptide on the basis of the N-terminal sequence of the native peptide. The 21-kd protein will be an important antigen for studies on the epidemiology, diagnosis, and pathogenesis of PBD.

Cytokine mRNA Expression in Isocyanate-Induced Hypersensitivity Pneumonitis

Background: Diisocyanate is widely used as a polymerizing agent for manufacturing many products. However, repeated inhalation exposure to diisocyanates in the workplace can cause bronchial asthma, hypersensitivity pneumonitis (HP), and neoplasia. Objectives: In the current study, immunological tests were conducted to explore the mechanisms involved in the pathogenesis of diisocyanate-induced HP. Methods: Evaluations included 4 patients with diisocyanate-induced HP, 4 volunteers with current occupational exposure to diisocyanates and 4 normal volunteers without a history of exposure to diisocyanates. IgG and IgA antibody levels to diisocyanates were determined by ELISA in sera and BAL fluids. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence or in the absence of 10 µg/ml MDI-HSA (4, 4′ diphenylmethane diisocyanate)-HSA (human serum albumin). 3H-thymidine uptake, mRNA expression by RT-PCR (beta-actin, IL-1beta, IL-2R, IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha, TGF-beta) were estimated. Results: Patients with diisocyanate-induced HP had detectable IgG and IgA antibodies to diisocyanates. In addition, PBMCs from HP patients proliferated in the presence of diisocyanates and showed enhanced expression of mRNA of proinflammatory cytokines. In contrast, normal volunteers with current occupational exposure showed elevated levels of mRNA expression of IL-10 and IL-2R, suggesting the presence of sensitized cells and protection from pathology as a result of enhanced IL-10 production. Conclusions: Patients with diisocyanate-induced HP are likely to override the protective effects of IL-10 as they express lower levels of this cytokine.

Identification of fungal DNA in BALF from patients with home-related hypersensitivity pneumonitis

BACKGROUND In Japan, a major type of home-related hypersensitivity pneumonitis (HP) is summer-type HP, which is caused by Trichosporon asahii (T. asahii) or Trichosporon mucoides. Some patients with home-related HP test negative for antibodies against Trichosporon; yet, a causative mold antigen cannot be identified. METHODS We analyzed 19 patients with home-related HP, 8 healthy volunteers, and 35 patients with other diseases. We extracted DNA from cell pellets of bronchoalveolar lavage fluid (BALF), amplified the DNA by PCR using Trichosporon-specific primers or other fungus-specific primers, and cloned as well as sequenced the PCR amplicon. Other primers used were specific for Acremonium chrysogenum, Aspergillus fumigatus, Aspergillus niger, Fusarium napiforme, Humicola fuscoatra, Penicillium corylophilum, and Pezizia domiciliana. RESULTS We detected Trichosporon DNA (n = 17) and F. napiforme DNA (n = 2) by PCR in 19 patients with home-related HP; however, these species were not identified in healthy volunteers. After sequencing of the PCR amplicon for Trichosporon species, we identified T. asahii (n = 11), Trichosporon japonicum (n = 1), and Cryptococcus uzbekistanesis (n = 4). CONCLUSION We could detect fungal DNA in BALF cell pellets from patients with home-related HP. These data suggest that this method might be useful to detect antigens responsible for home-related HP.

Synthetic double-stranded RNA enhances airway inflammation and remodelling in a rat model of asthma

Respiratory viral infections are frequently associated with exacerbations of asthma. Double‐stranded RNA (dsRNA) produced during viral infections may be one of the stimuli for exacerbation. We aimed to assess the potential effect of dsRNA on certain aspects of chronic asthma through the administration of polyinosine‐polycytidylic acid (poly I:C), synthetic dsRNA, to a rat model of asthma. Brown Norway rats were sensitized to ovalbumin and challenged three times to evoke airway remodelling. The effect of poly I:C on the ovalbumin‐induced airway inflammation and structural changes was assessed from bronchoalveolar lavage fluid and histological findings. The expression of cytokines and chemokines was evaluated by real‐time quantitative reverse transcription PCR and ELISA. Ovalbumin‐challenged animals showed an increased number of total cells and eosinophils in bronchoalveolar lavage fluid compared with PBS‐challenged controls. Ovalbumin‐challenged animals treated with poly I:C showed an increased number of total cells and neutrophils in bronchoalveolar lavage fluid compared with those without poly I:C treatment. Ovalbumin‐challenged animals showed goblet cell hyperplasia, increased airway smooth muscle mass, and proliferation of both airway epithelial cells and airway smooth muscle cells. Treatment with poly I:C enhanced these structural changes. Among the cytokines and chemokines examined, the expression of interleukins 12 and 17 and of transforming growth factor‐β1 in ovalbumin‐challenged animals treated with poly I:C was significantly increased compared with those of the other groups. Double‐stranded RNA enhanced airway inflammation and remodelling in a rat model of bronchial asthma. These observations suggest that viral infections may promote airway remodelling.

Serodiagnosis of Mycobacterium avium Complex Pulmonary Disease in Rheumatoid Arthritis

Background:Mycobacterium avium complex (MAC) pulmonary disease (PD) is often difficult and complicated to diagnose or to discriminate from follicular bronchitis, bronchiectasis, or other conditions associated with rheumatoid arthritis (RA) lung in the clinical setting. Objective: We investigated whether a serologic test for anti-glycopeptidolipid (GPL) antibody was useful for distinguishing MAC-PD from RA lung in diagnosis. Methods: Serum IgA antibody to MAC-specific GPL core antigen was measured by an enzyme immunoassay. Antibody levels were measured in sera from 14 RA patients with MAC-PD (RA + MAC), 20 RA patients with bronchial or bronchiolar lesions without MAC-PD (RA w/o MAC), 20 RA patients without pulmonary lesions (RA only), and 25 healthy volunteers (HV). Results: The levels of serum anti-GPL antibodies were higher in the RA + MAC group than in the RA w/o MAC, RA-only, and HV groups (2.87 ± 2.83 vs. 0.50 ± 0.45, 0.31 ± 0.24, and 0.38 ± 0.10 U/ml, respectively; p < 0.001). With the cutoff point in receiver-operating characteristic analysis set at 0.7 U/ml, the serologic test differentiated RA + MAC from RA w/o MAC with a sensitivity of 100% and specificity of 90%. Conclusions: This serologic test for anti-GPL antibody is useful for diagnosing MAC-PD in RA.

Bronchiolitis obliterans organising pneumonia syndrome presenting with neutrophilia in bronchoalveolar lavage fluid after breast-conserving therapy.

A 61-year-old female presented with a dry cough and fever 4 months after tangential radiation therapy (RT) following conserving surgery for breast cancer. Chest radiography and CT demonstrated consolidation with air bronchogram outside the irradiated area. Neutrophil granulocytes were abundant in bronchoalveolar lavage fluid (BALF) (39.6% of total cells), and transbronchial lung biopsy revealed organising pneumonia (OP) histologically. Antibiotic therapy had no effect, but corticosteroid therapy brought about clinical improvement. Her condition was diagnosed as bronchiolitis obliterans OP (BOOP) syndrome. Lymphocytic BALF has been identified as a characteristic of BOOP syndrome induced after RT for breast cancer. The BALF in this case, however, was neutrophilic. In our analysis of differential cell counts in the BALF of 24 patients with BOOP syndrome, the BALF was neutrophilic (>5%) in 16 (76%) cases, and the neutrophilia was severe in some of those patients.

Muscle weakness in extremities and diffuse centrilobular nodules in lungs

A 72-year-old female was admitted to our hospital because of abnormal lung shadows. Two years before admission, she had complained of paraesthesia in her hands. A gait disturbance appeared a year later and gradually worsened resulting in her losing the ability to walk altogether. She had also become constipated and developed a urinary disorder. She had undergone total gastrectomy for gastric cancer 15 years ago and had received a blood transfusion at that time. On physical examination, she presented with muscle weakness in all four extremities, thermal hypoesthesia, an inability to sense vibration and dysautonomia. She had no fever. Laboratory findings indicated high lysozyme. Purified protein derivative (PPD) skin test was negative (table 1). MRI revealed T2 high-intensity areas in the …