Eosinophilic tracheobronchitis and airway cough hypersensitivity in chronic non-productive cough

BACKGROUND: We have shown that some patients presenting with chronic bronchodilator-resistant non-productive cough have global atopic tendency and airway cough hypersensitivity without non-specific bronchial hyperresponsiveness, abbreviated as atopic cough. The cough is successfully treated with histamine H1-antagonists and/or glucocorticoids. OBJECTIVE: This prospective study was conducted to elucidate the histological feature of atopic cough. METHODS: Tracheal and bronchial mucosa obtained by transbronchoscopic biopsy and bronchoalveolar lavage (BAL) cell component were studied with special emphasis on eosinophils in eight non-smokers diagnosed with atopic cough, all of whom had increased sensitivity of cough response to inhaled capsaicin, normal lung function and bronchial responsiveness to methacholine and normal chest roentgenogram. Their cough completely resolved on histamine H1-antagonists and/or glucocorticoids. Transbronchoscopic tracheal and bronchial biopsy and BAL were also performed in healthy non-smokers as a control. RESULTS: A small number of eosinophils was detected in subepithelium of trachea in six of seven patients and in subepithelium of bronchi in seven of eight cough patients. The numbers of eosinophils in subepithelium of trachea and bronchi were significantly increased in the patients compared with control subjects. There was no BAL eosinophilia in any patients. CONCLUSION: It is concluded that eosinophilic tracheobronchitis and cough hypersensitivity are pathological and physiological characteristics of atopic cough.     

Herpes simplex lymphadenitis: a case report and review of the published work.

Viral lymphadenitis may lead to a histological appearance that can simulate malignancy. The histological features of herpes simplex lymphadenitis have not previously been described in detail. We report a case of proved herpes simplex lymphadenitis in a 30 year old man which was characterised by a pronounced proliferation of immunoblasts. The microscopical findings are described and the published work is reviewed.     

Necrotizing Tracheobronchitis: A complication of high frequency jet ventilation

Summary The tracheal and bronchial lesions observed are described in seven patients, presenting with respiratory distress syndrome and receiving both conventional and high frequency jet ventilation for various periods. The histological findings are related to the duration of the exposure as well as the number of pulsations administered to the tracheobronchial tree. Severe damage to the mucosa leading to acute tracheobronchitis, hyperplasia and hypersecretion of the mucosal glands may explain some of the clinical symptoms observed, especially the upper respiratory obstruction. Care should be taken to limit these changes which may lead to various degrees of stenosis in survivors receiving this mode of therapy.     

Simultaneous cytological diagnosis of herpes simplex virus infection and primary lung cancer: report of two cases

Herpes simplex is an uncommon cause of lower respiratory tract infection that requires prompt diagnosis and treatment to prevent late complications. We report two cases with simultaneous herpes simplex virus infection of the lower respiratory tract and lung carcinoma. Cytology of bronchial brushing and washing fluids and postbronchoscopic sputum established the diagnosis, which was further corroborated by real-time polymerase chain reaction.     

Frequency of "blue bodies" in pulmonary cytology specimens

To determine the frequency of occurrence of "blue bodies" (BBs), 2,010 pulmonary cytology specimens (1,403 sputum and 607 bronchial specimens) from 1985 were reviewed. The smears were examined microscopically by transmitted and polarized light. BBs were extracellular structures, occurring most commonly in clusters but sometimes conglomerated. With Papanicolaou stain, they had a characteristic birefringent laminated brown core and a nonbirefringent blue rim. Chemical microanalysis and energy-dispersive x-ray analysis revealed that their chemical composition was calcium carbonate. A total of 233 specimens contained BBs, with a frequency of 10.5% in bronchial specimens and 12% in sputum. Only 8.6% of the BBs had co-existent pulmonary malignancy. We concluded that BBs were common structures in pulmonary cytology and were not associated with pulmonary malignancy or pulmonary fibrosis in our series. They must be distinguished from contaminants, staining artifacts, and parasitic ova.     

The histopathology of the upper airway in the neonate following mechanical ventilation

Laryngotracheobronchial lesions were carefully documented in 26 neonatal autopsies and were classified into two main types. Type I lesions were focal desquamative or ulcerative, asynchronous, and variable in severity involving areas exposed to contact with endotracheal tube or suction catheter. These lesions are most likely due to trauma of artificial ventilation. Type II lesions were diffuse, necrotizing, more synchronous and uniform in severity involving tissues distal to the endotracheal tube and extending to second or third generation bronchi. The early or mild type II lesions consisted of coagulative necrosis of epithelial cells and mucosal oedema. The late or severe type II lesions showed features similar to those of necrotizing tracheobronchitis described by Metley et al. All the cases with type II lesions had been ventilated with 100 per cent oxygen continuously for at least 3 h during life. The use of pure oxygen may be an important factor leading to necrotizing tracheobronchitis.     

Exercise-induced bronchial lability in monozygotic (identical) and dizygotic (nonidentical) twins

Exercise tests and skin tests were carried out on 8 pairs of identical and 7 pairs of nonidentical twins. The pairs of twins were selected so that at least one member of each pair had clinical asthma or was a first-degree relative of a patient with asthma and had an increased bronchial lability on exercise. Clinical concordance for active asthma was found in 3 of the identical pairs but only one of the nonidentical pairs. In 2 further identical pairs, one subject had active asthma and the other had a past history of asthma. In 6 of the identical pairs, the other twin was also found to have an increased bronchial lability, while only one of the nonidentical pairs was concordant in this respect. From the point of view of atopy shown by skin tests, 6 identical pairs were concordant compared with one of the nonidentical pairs. Concordance for atopy and bronchial lability did not necessarily go together. The significantly higher rate of concordance among the identical twins, for both increased bronchial lability and atopy, shows the importance of inheritance for these characters.     

Electromagnetic navigation bronchoscopy‐guided fine needle aspiration for the diagnosis of lung lesions

Many peripheral lung lesions are beyond the reach of conventional bronchoscopes, and require percutaneous CT‐guided or open surgical biopsy, which carry increased risks to the patient. Electromagnetic navigation bronchoscopy (ENB) is a relatively new technique, which uses an image guided localization system to direct steerable bronchoscopic tools to predetermined points within the bronchial tree. This technology allows improved access to peripheral lesions in particular. We investigated the sensitivity and specificity of ENB‐guided fine needle aspiration (FNA) in the diagnosis of lung lesions. All ENB‐guided FNAs performed at one institution were included in the study. The superDimension i‐Logic System? was used in all cases. Pathologic reports of the ENB‐guided FNAs, as well as all other pulmonary sampling performed simultaneously with the FNA and within 1 year of the ENB‐guided FNA were reviewed. Patients with a positive ENB‐guided FNA or malignancy within the same lobe within the follow‐up period were considered positive for malignancy. Patients with an atypical diagnosis but no definitive malignancy were considered negative for malignancy for statistical purposes. Ninety‐one patients underwent 95 ENB‐guided FNAs over a 3‐year period. Thirty‐five patients (38%) were positive for malignancy. ENB‐guided FNA had a sensitivity of 63% for the detection of malignancy. The sensitivity for the detection of malignancy using all ENB‐guided sampling methods, including FNA, bronchoscopic biopsy, and bronchial brushing was 83%. Pathologists and cytotechnologists should be aware of ENB‐guided FNA as an emerging technology with a relatively high sensitivity for the diagnosis of peripheral lung lesions. Diagn. Cytopathol. 2014;42:1045–1050. © 2014 Wiley Periodicals, Inc.     

Flow cytometric analysis of pulmonary fluids and cells for the detection of malignancies.

Cells from a pulmonary or bronchial origin were analyzed with flow cytometry to assess the sensitivity and specificity of this method in diagnosing malignancy. In all instances, cells submitted for flow cytometry analysis were excess cells from specimens submitted for routine cytology. Less than 3% of all samples were rejected for insufficient material. Overall sensitivity from all sources was 86%, specificity 96%. Although cytology results were the standard for determining accuracy of flow cytometry, in a few patients cytology appeared normal and initial evidence for malignancy was obtained from flow cytometry. For this reason, flow cytometry may be a valuable adjunctive technology in the diagnosis of malignancy.     

Asthma caused by occupational exposure to a furan-based binder system

A 50-yr-old mold maker developed severe asthma a few weeks after commencing work with a furan binder. Asthma recurred within hours of subsequent exposure and was confirmed by measurements every 2 hr of peak flow rate. The molds were prepared by mixing sand with a resin (containing furfuryl alcohol, paraformaldehyde, and xylene) and a catalyst (containing sulfuric acid, phosphoric acid, and butyl alcohol). Occupation-type exposure in the laboratory to the resin mixed with catalyst, and to pure furfuryl alcohol mixed with sulfuric acid or butyl alcohol, provoked late asthmatic responses and heightened nonallergic bronchial responsiveness to inhaled histamine. No changes were produced by the same exposures in an asthmatic volunteer with a similar degree of histamine bronchial responsiveness, or in the worker after exposure to resin alone and catalyst alone. Avoidance of exposure was followed by clearing of symptoms and return of histamine bronchial responsiveness towards normal. The findings identify the occurrence of specific bronchial responsiveness to volatile reaction product(s) of furfuryl alcohol following reaction with sulfuric acid or with butyl alcohol. The incidence of this problem needs investigation, especially since furan-based binder systems are replacing traditional methods.     

Accidental transplantation of bronchial carcinoma from a cadaver donor to two recipients of renal allografts.

Malignancy was transferred inadvertently to two patients, each of whom received a renal transplant from a cadaver donor who was found at necropsy to have a small, clinically silent carcinoma of lung. Both recipients died with metastatic bronchial carcinoma of the same histological type as the donor's tumour. The literature on transplanted malignancy is reviewed.     

Plastic bronchitis and mucoid impaction--uncommon disease syndromes with expectoration mucus plugs

Mucoid impaction and plastic bronchitis are relatively rare disorders caused by the formation of obstructive airway plugs. We observed from February 1999 to June 2000 seven patients with mucoid impaction and one with plastic bronchitis. In the group of mucoid impaction there were 4 patients with bronchial asthma and 3 without history of lung disease. At the admission to hospital all patients suffered from cough, chest pain and effort dyspnea. Two of them expectorated during cough "bronchial casts". The chest X-ray of 5 patients revealed atelectasis of one of the lung's lobes and diffuse opacities in 2 others. In 4 cases during bronchoscopy one bronchus and in another three--numerous bronchi were obstructed with mucoid casts. Removing of the casts caused both the improvement of the patients' condition and withdrawal of atelectasis in 4 cases. In 5 patients the final diagnosis was allergic bronchopulmonary aspergillosis and in two mucoid impaction in the course of asthma without aspergillosis. Plastic bronchitis was observed in 44 years old man, who expectorated white, branching, bronchial casts for three months. On admission he was in respiratory failure. The chest X-ray revealed diffuse alveolar infiltrates and HRCT glass-ground opacities in both lungs and bronchiectasis in the middle lobe. The bronchofiberoscopy disclosed diffuse tracheobronchitis with casts occluding the middle lobe bronchus. Microscopic examination of the removed casts showed aggregates of mucus, macrophages, neutrophils and cells of respiratory epithelium. Precipitins against Aspergillus fumigatus were not found. Staphyloccocus coagulase (-) was cultured from urine and sputum specimens. We administered Vancomycin with Netylmycin, acetylocysteine, oxygen therapy and humid inhalation and the patient recovered. HRCT made six months after admission revelated total withdrawal of glass-ground opacities. The pathogenesis of plastic bronchitis in this case was unclear.     

Effect of histamine and methacholine on nasal airway resistance in atopic and nonatopic subjects: Comparison with bronchial challenge and skin test responses

Serial nasal, intracutaneous, or bronchial challenges were carried out with solutions containing 2- or 3-fold increments in histamine (H) or methacholine (Meth) concentration until nasal airway resistance (NAR) increased by more than 100%, a large intracutaneous reaction was elicited, or FEV₁ decreased by 20% or more. Thirty nonatopic and 48 asymptomatic atopic subjects were studied, the latter group divided into rhinitic patients with and without asthma. Several types of data analysis demonstrated there was no significant difference in the nasal or cutaneous effects of H or Meth between the atopic and nonatopic groups. Comparable results were obtained in a subgroup of 39 subjects (13 normal, 13 atopic, and 13 atopic with asthma) who underwent all six test sequences (i.e., nasal, cutaneous, and bronchial with both drugs). As expected, the asthmatics showed significantly increased bronchial reactivity to both agents. In comparison with Meth, H had a much greater effect on the nasal mucosa and skin than on the bronchi. It is concluded that, contrary to bronchial responses, but in accord with cutaneous reactivity, the nasal responses of nonatopic subjects, atopic persons with allergic rhinitis alone, and subjects with both allergic rhinitis and asthma show no intergroup differences on testing with H or Meth.     

Prazosin, an alpha1-adrenoceptor antagonist, partially inhibits exercise-induced asthma

The effect of prazosin, a potent and specific alpha 1-adrenoceptor antagonist given by inhalation (total nebulized 2 mg) was compared with placebo in a double-blind randomized study of 10 atopic asthmatic children. Prazosin significantly (p less than 0.01) reduced the severity of post-exercise bronchoconstriction (maximum fall in peak expiratory flow after exercise 21.4% +/- SEM 6.3% after prazosin compared with 42.5% +/- 7.3% after placebo). This protective action of prazosin suggests that activation of alpha 1-adrenoceptor may be involved in the pathogenesis of exercise-induced asthma either by facilitation of mast-cell mediator release or by direct contraction of bronchial smooth muscle. Prazosin did not significantly change resting bronchomotor tone or histamine-induced bronchoconstriction, suggesting no effect on bronchial smooth muscle contractility.     

Infections in the gastrointestinal tract that can mimic malignancy

Infections in the gastrointestinal tract can present with the clinical impression of malignancy. These infectious mimics can take on a variety of forms from endoscopically concerning ulcers to large infiltrative masses and may be associated with lymphadenopathy and distant disease that is concerning for metastasis. In such cases, histopathology plays a key role in rendering a diagnosis of infection. In this review, we summarize the common and rare gastrointestinal infectious mimics of malignancy reported in the English medical literature. Microorganisms of all types have been implicated including bacteria, viruses, fungi, and parasites. Common bacterial causes include tuberculosis, actinomycosis, syphilis, and lymphogranuloma venereum. A small number of cases are due to other bacteria such as Helicobacter, Yersinia, α-hemolytic Streptococcus and Rhodococcus. The most common viral mimic of malignancy is cytomegalovirus; however, herpes simplex virus and Epstein-Barr virus have also been reported. Frequent fungal causes include histoplasmosis, mucormycosis and basidiobolomycosis; with a small number of cases due to candidiasis, aspergillosis and paracoccidiomycosis. Parasitic mimics of malignancy are less common. They include mostly protozoal infection such as amebiasis; however, a handful of various helminth infections (anisakiasis, strongyloidiasis, enterobiasis, trichuriasis, schistosomiasis, fascioliasis, echinococcosis) have also been reported. In summary, infectious etiology should be considered in the differential diagnosis of lesions in the gastrointestinal tract that are suspicious for malignancy.     

Mucinous carcinoma (colloid carcinoma) of the lung diagnosed by fine needle aspiration cytology: a case report

Mucinous carcinoma of the lung, also known as colloid carcinoma, is an uncommon tumour that is rarely encountered in fine needle aspiration (FNA) cytological practice. A 64-year-old Chinese male presenting with blood stained sputum and hoarseness of voice was discovered to have a 3 cm sized mass in the left lung. Neither bronchial washings nor transthoracic FNA yielded positive results at this stage. Six months later the patient returned to the hospital with a larger tumour and mediastinal lymphadenopathy. Transbronchial lymph node FNA, reported as negative for malignancy showed normal, hyperplastic and mildly atypical bronchial epithelial cells as well as a few single cells and extracellular mucin. Transthoracic FNA of the lung lesion performed under computed tomographic guidance showed characteristic cytological features of this tumour, establishing the diagnosis.     

Further studies on the mechanism of human histamine-induced asthma : The effect of an aerosolized H1 receptor antagonist (diphenhydramine)

This study was designed to better define the mechanism of histamine-induced bronchoconstriction in humans by pharmacologic manipulation of the postulated bronchial histamine receptor sites. Histamine challenges were performed on a heterogeneous group of adult asthmatic subjects. The cumulative units of histamine required for induction of a sustained 20% or greater decrease in FEV1 from baseline were determined. The effect of pretreatment with an aerosolized H1 receptor antagonist, diphenhydramine hydrochloride, was then studied. Analysis of the data showed that the administration of an H1 receptor antagonist prior to histamine challenge significantly blocked the bronchial response to histamine (p less than 0.005). This effect was considered to be due to specific competitive antagonism at the H1 receptor site and suggests the presence of H1 receptors in human bronchial mucosa.     

Effect of immunotherapy in chronic asthmatic children

Ten children with chronic intractable asthma whose airway sensitivity had been established by means of inhalation challenges to specific antigens were hyposensitized over a period of 5 to 12 months. Five additional asthmatic children acted as “controls.” Various aqueous antigens were used both for immunotherapy and for inhalational challenges. Therapy was given uninterruptedly. The total dose varied from 1,000 to 8,000 protein nitrogen units (PNU) in the controls and from 30,000 to 230,000 PNU in the subjects. Repeat challenges in the low-dose “control” group showed no changes in bronchial sensitivity. Ten children who received high total dosage all showed decreased bronchial sensitivity to specific antigens. Three children who were under study for 12 months could be evaluated clinically as well as physiologically since all four seasons were covered. There was no evidence of clinical, physiologic, or medication improvement in any of them, despite significant decreases in bronchial sensitivity. High-dose therapy appeared to decrease bronchial sensitivity significantly in all except two subjects. The effect was not related to the antigen dose but appeared to be an individual response of the subject.     

Miliary tuberculosis in pregnancy.

Although miliary tuberculosis is uncommon in pregnancy, it is difficult to diagnose when present and is often associated with a maternal history of intravenous drug abuse, malignancy, alcoholism, or human immunodeficiency virus infection. This article reports two antepartum cases of miliary tuberculosis without any of these risk factors. Bronchial washings for Pneumocystis carinii and HIV screening were negative for both patients. Acid-fast bacilli stains of the bronchial washing and ascitic fluid were also negative. Several weeks were required for ascitic fluid and bronchial biopsy Mycobacterium cultures to be positive. In contrast, acid-fast bacilli were seen within 24 hours in multiple sections of the delivered placentas. Confirming the diagnosis of miliary tuberculosis is an arduous process requiring a high index of suspicion. During pregnancy, pathologic examination of tissue obtained by placental biopsy may facilitate making an early diagnosis of extrapulmonary tuberculosis.     

Immunologic and nonimmunologic mechanisms in asthma due to western red cedar (Thuja plicata)

Occupational asthma due to western red cedar (Thuja plicata) is the most common form of occupational asthma in British Columbia, occurring in about 5% of the exposed workers. Plicatic acid, uniquely present in western red cedar, was found to be the agent responsible for the asthmatic reactions. Inhalation provocation tests with an extract of western red cedar or plicatic acid induced late asthmatic reactions alone in 44%, dual (immediate and late) reactions in 49%, and immediate reactions alone in 7% of the 185 patients. Of the 75 patients who left the industry and were no longer exposed to the wood, only 50% recovered completely after an average period of 3 yr; the remaining half continued to have recurrent attacks of asthma. Specific IgE antibodies to crude red cedar extract or plicatic acid-human serum albumin conjugate were found in less than 40% of the patients by the RAST, while IgG antibodies were not detected. There was no correlation between the presence and absence of specific IgE antibodies and the type of asthmatic reaction induced during inhalation challenge. IgE antibodies were not found in exposed subjects with no asthmatic reaction on inhalation challenge. There was significant correlation between the degree of nonspecific bronchial hyperreactivity and the degree of bronchial reactivity to plicatic acid during immediate or late asthnatic reactions. The degree of nonspecific bronchial hyperreactivity was increased after late asthmatic reactions induced by plicatic acid. On the other hand, the degree of nonspecific bronchial hyperreactivity was reduced and gradually returned to normal among patients who became asymptomatic after exposure was discontinued. These findings suggest that nonspecific bronchial hyperreactivity plays an important role in the pathogenesis of red cedar asthma. The mechanism of bronchial hyperreactivity induced by red cedar exposure is unknown; an immunologic mechanism may be important. Direct release of histamine from human basophils and mast cells and direct activation of the complement system by plicatic acid are unlikely pathogenetic mechanisms.