BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

BACKGROUND: Metalworking fluids (MWFs) are mixtures with inhalation exposures as mists, dusts, and vapors, and dermal exposure in the dispersed and bulk liquid phase. A quantitative risk assessment was performed for exposure to MWF and respiratory disease.METHODS: Risks associated with MWF were derived from published studies and NIOSH Health Hazard Evaluations, and lifetime risks were calculated. The outcomes analyzed included adult onset asthma, hypersensitivity pneumonitis, pulmonary function impairment, and reported symptoms. Incidence rates were compiled or estimated, and annual proportional loss of respiratory capacity was derived from cross-sectional assessments.RESULTS: A strong healthy worker survivor effect was present. New-onset asthma and hypersensitivity pneumonitis, at 0.1 mg/m3 MWF under continuous outbreak conditions, had a lifetime risk of 45%; if the associated microbiological conditions occur with only 5% prevalence, then the lifetime risk would be about 3%. At 0.1 mg/m3, the estimate of excess lifetime risk of attributable pulmonary impairment was 0.25%, which may have been underestimated by a factor of 5 or more by a strong healthy worker survivor effect. The symptom prevalence associated with respiratory impairment at 0.1 mg/m3 MWF was estimated to be 5% (published studies) and 21% (Health Hazard Evaluations).CONCLUSION: Significant risks of impairment and chronic disease occurred at 0.1 mg/m3 for MWFs in use mostly before 2000. Evolving MWFs contain new ingredients with uncharacterized long-term hazards.
Adult ; Alveolitis, Extrinsic Allergic ; Asthma ; Asthma, Occupational ; Chronic Disease ; Dust ; Humans ; Incidence ; Inhalation Exposure ; National Institute for Occupational Safety and Health (U.S.) ; Prevalence ; Risk Assessment ; Survivors

Adult ; Alternaria ; immunology ; Alveolitis, Extrinsic Allergic ; immunology ; Animals ; Antibodies ; immunology ; Antibodies, Bacterial ; immunology ; Antibodies, Fungal ; immunology ; Antigens ; immunology ; Antigens, Bacterial ; immunology ; Antigens, Fungal ; immunology ; Aspergillus fumigatus ; immunology ; Asymptomatic Diseases ; Candida albicans ; immunology ; Cladosporium ; immunology ; Columbidae ; immunology ; Female ; Healthy Volunteers ; Humans ; Immunoglobulin G ; immunology ; Male ; Melopsittacus ; immunology ; Middle Aged ; Mucor ; immunology ; Nocardia ; immunology ; Parrots ; immunology ; Penicillium chrysogenum ; immunology ; Stachybotrys ; immunology ; Thermoactinomyces ; immunology

Drug-induced hypersensitivity pneumonitis results from interactions between pharmacologic agents and the human immune system. We describe a 54-year-old man with hypersensitivity pneumonitis caused by cephalosporins with identical R1 side chains. The patient, who complained of cough with sputum, was prescribed ceftriaxone and clarithromycin at a local clinic. The following day, he complained of dyspnea, and chest X-ray revealed worsening of inflammation. Upon admission to our hospital, antibiotics were changed to cefepime with levofloxacin, but his pneumonia appeared to progress. Changing antibiotics to meropenem with ciprofloxacin improved his symptoms and radiologic findings. Antibiotics were de-escalated to ceftazidime with levofloxacin, and his condition improved. During later treatment, he was mistakenly prescribed cefotaxime, which led to nausea, vomiting, dyspnea and fever, and indications of pneumonitis on chest X-ray. We performed bronchoalveolar lavage, and the findings included lymphocytosis (23%), eosinophilia (17%), and a low cluster of differentiation (CD) 4 to CD8 ratio (0.1), informing a diagnosis of drug-induced pneumonitis. After a medication change, his symptoms improved and he was discharged. One year later, he was hospitalized for acute respiratory distress syndrome following treatment with ceftriaxone and aminoglycosides for an upper respiratory tract infection. After steroid therapy, he recovered completely. In this patient, hypersensitivity reaction in the lungs was caused by ceftriaxone, cefotaxime, and cefepime, but not by ceftazidime, indicating that the patient's hypersensitivity pneumonitis was to the common R1 side chain of the cephalosporins.
Alveolitis, Extrinsic Allergic* ; Aminoglycosides ; Anti-Bacterial Agents ; Bronchoalveolar Lavage ; Cefotaxime ; Ceftazidime ; Ceftriaxone ; Cephalosporins* ; Ciprofloxacin ; Clarithromycin ; Cough ; Diagnosis ; Drug-Related Side Effects and Adverse Reactions ; Dyspnea ; Eosinophilia ; Fever ; Humans ; Hypersensitivity ; Immune System ; Inflammation ; Levofloxacin ; Lung ; Lymphocytosis ; Middle Aged ; Nausea ; Pneumonia ; Respiratory Distress Syndrome, Adult ; Respiratory Tract Infections ; Sputum ; Thorax ; Vomiting

M. immunogenum was identified as the etiologic agent of a variety of hospital-acquired infections, including an outbreak of keratitis, and as the potential cause of hypersensitivity pneumonitis in industrial metal-grinding machinists. This microorganism appears to differ from other members of the M. chelonae?abscessus group. Clinically significant isolates have been recovered from skin lesions, corneal ulcers, joint fluid, central venous catheter sites, and blood. There have been some cases of M. immunogenum skin infection reported. We report a suspected case of cutaneous Mycobacterium immunogenum infection in a 23-year-old male, migrant Workers from Sri Lanka, who presented with an erythematous plaque on his right ear. M. immunogenum was suspected by PCR-restriction fragment length polymorphism & sequencing of PCR product. The patient was treated with clarithromycin & ofloxacin. The lesion started to improve 4 weeks after initiation of the therapy. We have the patient in therapy for 3 months, and the lesion is slowing disappeared.
Alveolitis, Extrinsic Allergic ; Central Venous Catheters ; Clarithromycin ; Ear ; Humans ; Joints ; Keratitis ; Male ; Mycobacterium* ; Ofloxacin ; Polymerase Chain Reaction ; Skin ; Sri Lanka ; Transients and Migrants ; Ulcer ; Young Adult

BACKGROUND: Cellular analysis of bronchoalveolar lavage fluid (BALF) is a useful diagnostic tool for interstitial lung diseases (ILDs). The lymphocytes in BALF consist of CD3+CD4+ T cells (T4), CD3+CD8+ T cells (T8), and a few B cells. However, sometimes, an increased number of CD3+CD4-CD8- T cells (double-negative T cells, DNTs) are noted in BALF. It is known that DNTs in the blood are associated with immunoregulation and autoimmune diseases. However, there are only few studies on DNTs in BALF. We evaluated the DNTs in BALF in patients with pulmonary diseases. METHODS: Immunophenotyping results of the BALF obtained from 122 pulmonary disease patients over an 8-yr period were reviewed. T-lymphocyte subsets (T4, T8, and DNT) and inflammatory markers were analyzed for each group of clinical diagnosis. T-lymphocyte percentage of more than 15% of the total cells was defined as BALF lymphocytosis, and DNT percentage of more than 5% of T lymphocytes was defined as high DNT. RESULTS: The most frequent diseases found in the patients were pneumonia (31.6%), autoimmune-related ILDs (18.0%), hypersensitivity pneumonitis (10.7%), and organizing pneumonia (10.7%). However, the occurrence of autoimmune-related ILDs was significantly high (40%) in patients with lymphocytosis and high DNT (P=0.002). All lung cancer patients showed lymphocytosis with high DNT. In addition, CD3-signal intensities of DNTs were significantly higher than those of other T-lymphocyte subtypes (P=0.003). CONCLUSION: The number of DNTs in BALF was increased in patients with autoimmune-related ILDs and lung cancer. High DNTs in BALF are useful as supportive diagnostic tools for autoimmune-related ILDs.
Alveolitis, Extrinsic Allergic ; Autoimmune Diseases ; B-Lymphocytes ; Bronchoalveolar Lavage Fluid* ; Diagnosis* ; Humans ; Immunophenotyping ; Lung Diseases* ; Lung Diseases, Interstitial ; Lung Neoplasms ; Lymphocytes ; Lymphocytosis ; Pneumonia ; T-Lymphocyte Subsets ; T-Lymphocytes*

Alveolitis, Extrinsic Allergic ; chemically induced ; Humans ; Triazines ; adverse effects

A patient treated with venlafaxine for major depression developed an interstitial lung disease (ILD) with the characteristic clinical, radiological and pathological features of chronic hypersensitivity pneumonitis. A high resolution computed tomography scan demonstrated ground glass opacity, mosaic perfusion with air-trapping and traction bronchiectasis in both lungs. The pathological findings were consistent with a nonspecific interstitial pneumonia pattern. Clinical and radiological improvements were noted after the discontinuation of venlafaxine and the administration of a corticosteroid. This report provides further evidence that the anti-depressant venlafaxine can cause ILD.
Alveolitis, Extrinsic Allergic ; Bronchiectasis ; Depression ; Glass ; Humans ; Hypersensitivity ; Lung ; Lung Diseases, Interstitial* ; Perfusion ; Pneumonia ; Traction ; Venlafaxine Hydrochloride

PURPOSE: Asthma is a chronic respiratory disorder that leads to inflammation and narrowing of the airways. Its global prevalence has attained epidemic levels and treatment options that reach beyond temporary relief of symptoms are urgently needed. Since the processes leading to clinically symptomatic asthma start early in life, we set out to systematically evaluate a neonatal immunotherapeutic based on Listeria monocytogenes (Lm) for the control of allergic sensitization. METHODS: We modified Lm to express the model allergen, ovalbumin (OVA), and tested the ability of neonatal immunization with this strain to control allergic sensitization in a mouse model of OVA-induced asthma. Mice were immunized as newborns with live or heat killed LmOVA or live Lm, followed 6 weeks later by allergic sensitization with OVA. In order to determine whether the T(H)1-polarizing effect of this vaccine vector inadvertently may exacerbate development of certain T(H)1-driven allergic diseases, mice immunized as newborns were assessed in a model of adult hypersensitivity pneumonitis (HP). RESULTS: Both LmOVA and Lm-control vaccines were highly effective in providing long-lasting protection from airway inflammation after only one immunization given perinatally. Serum antibody levels and lung cytokine production suggest that this prophylactic strategy is associated with an allergen specific T(H)1-dominated response. Specifically, LmOVA vaccinated mice displayed significantly elevated OVA-specific serum IgG2a, but no difference in anti-OVA IgE antibodies and only slightly decreased anti-OVA IgG1 antibodies. Importantly, Lm-based neonatal vaccination did not exacerbate Th1/Th17 driven HP, arguing against broad spectrum immune skewing. CONCLUSIONS: Our findings highlight the promise of early life Lm-based immunomodulatory interventions as a prophylactic strategy for allergic asthma.
Adult ; Alveolitis, Extrinsic Allergic ; Animals ; Antibodies ; Asthma ; Hot Temperature ; Humans ; Immune System ; Immunization* ; Immunoglobulin E ; Immunoglobulin G ; Infant, Newborn ; Inflammation* ; Listeria monocytogenes* ; Lung ; Mice ; Ovalbumin ; Ovum ; Prevalence ; Vaccination ; Vaccines

PURPOSE: Asthma is a chronic respiratory disorder that leads to inflammation and narrowing of the airways. Its global prevalence has attained epidemic levels and treatment options that reach beyond temporary relief of symptoms are urgently needed. Since the processes leading to clinically symptomatic asthma start early in life, we set out to systematically evaluate a neonatal immunotherapeutic based on Listeria monocytogenes (Lm) for the control of allergic sensitization. METHODS: We modified Lm to express the model allergen, ovalbumin (OVA), and tested the ability of neonatal immunization with this strain to control allergic sensitization in a mouse model of OVA-induced asthma. Mice were immunized as newborns with live or heat killed LmOVA or live Lm, followed 6 weeks later by allergic sensitization with OVA. In order to determine whether the T(H)1-polarizing effect of this vaccine vector inadvertently may exacerbate development of certain T(H)1-driven allergic diseases, mice immunized as newborns were assessed in a model of adult hypersensitivity pneumonitis (HP). RESULTS: Both LmOVA and Lm-control vaccines were highly effective in providing long-lasting protection from airway inflammation after only one immunization given perinatally. Serum antibody levels and lung cytokine production suggest that this prophylactic strategy is associated with an allergen specific T(H)1-dominated response. Specifically, LmOVA vaccinated mice displayed significantly elevated OVA-specific serum IgG2a, but no difference in anti-OVA IgE antibodies and only slightly decreased anti-OVA IgG1 antibodies. Importantly, Lm-based neonatal vaccination did not exacerbate Th1/Th17 driven HP, arguing against broad spectrum immune skewing. CONCLUSIONS: Our findings highlight the promise of early life Lm-based immunomodulatory interventions as a prophylactic strategy for allergic asthma.
Adult ; Alveolitis, Extrinsic Allergic ; Animals ; Antibodies ; Asthma ; Hot Temperature ; Humans ; Immune System ; Immunization* ; Immunoglobulin E ; Immunoglobulin G ; Infant, Newborn ; Inflammation* ; Listeria monocytogenes* ; Lung ; Mice ; Ovalbumin ; Ovum ; Prevalence ; Vaccination ; Vaccines