Abnormal vocal cord movement in patients with and without airway obstruction and asthma symptoms.

BACKGROUND: Abnormal vocal cord movements can cause laryngeal extrathoracic airway obstruction (often called vocal cord dysfunction - VCD) leading to asthma-like symptoms. These aberrant movements are characteristically present during inspiration and termed paradoxical vocal cord movement (PVCM). We have reported PVCM in up to 40% of severe asthmatics, but it is not known if PVCM is detectable in all patients with asthma-like symptoms and if the condition is more often associated with abnormal lung function. OBJECTIVE: We hypothesized that PVCM is frequently associated with asthma symptoms accompanied by airflow limitation. Studies examined whether PVCM is solely linked to experiencing asthma symptoms, or if PVCM is related to airflow limitation and/or other disease characteristics. METHODS: Patients with asthma symptoms were recruited from general practice and severe asthma clinics (n = 155). Pulmonary function measurements were conducted, asthma control and Nijmegen (dysfunctional breathing) questionnaires were administered and skin prick testing was carried out. PVCM was quantified using dynamic 320-slice computerized tomography of the larynx. Groups were divided into patients with FEV1 ≥ 80% predicted or FEV1 < 80% predicted and FEV1 /FVC < 0.7. ATS/ERS definitions of severity were also applied and evaluated. Detection of PVCM in the groups was compared and analyses performed to identify features associated with PVCM. RESULTS: Overall (n = 155), PVCM was detected in 42 cases (27.1%). Patients with FEV1 < 80% predicted had PVCM more often (25/68, 36.8%) than individuals with normal spirometry (17/87, 19.5%; P = 0.016). PVCM was associated with older age (P = 0.003) and with Nijmegen scores > 20 (P = 0.04). Patients with FEV1 < 80% predicted plus Nijmegen scores > 20 were more likely to have PVCM (OR = 9.3, P = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Paradoxical vocal cord movement is more often associated with asthma symptoms accompanied by airflow limitation and dysfunctional breathing. Further studies are needed to determine whether PVCM is induced by dysfunctional breathing practices and/or airway obstruction. How PVCM links with symptomatic asthma and VCD also requires evaluation.

Systemic humoral immunity to non-typeable Haemophilus influenzae.

Non-typeable Haemophilus influenzae (NTHi) is a major cause of respiratory but rarely systemic infection. The host defence to this bacterium has not been well defined in patients with chronic airway infection. The aim of this study was to assess the effect of humoral immunity in host defence to NTHi. Responses were measured in control and bronchiectasis subjects who had recurrent bronchial infection. Antibody and complement-mediated killing was assessed by incubating NTHi with serum and the role of the membrane-attack complex and classical/alternate pathways of complement activation measured. The effect of one strain to induce protective immunity against other strains was assessed. The effect of antibody on granulocyte intracellular killing of NTHi was also measured. The results showed that both healthy control subjects and bronchiectasis patients all had detectable antibody to NTHi of similar titre. Both groups demonstrated effective antibody/complement-mediated killing of different strains of NTHi. This killing was mediated through the membrane-attack complex and the classical pathway of complement activation. Immunization of rabbits with one strain of NTHi resulted in protection from other strains in vitro. Antibody activated granulocytes to kill intracellular bacteria. These findings may explain why NTHi rarely causes systemic disease in patients with chronic respiratory mucosal infection and emphasize the potential importance of cellular immunity against this bacterium.

Cytotoxic T lymphocyte and natural killer cell responses to non-typeable Haemophilus influenzae.

Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells have a key role in host defence against infectious pathogens, but their response to bacteria is not well characterized. Non-typeable Haemophilus influenzae is a major cause of respiratory tract infection including otitis media, sinusitis, tonsillitis and chronic bronchitis (especially in chronic obstructive pulmonary disease and bronchiectasis). This bacterium is also present in the pharynx of most healthy adults. The primary factor that may determine whether clinical disease occurs or not is the nature of the lymphocyte response. Here we examined the CTL cell and NK cell responses to nontypeable H. influenzae in healthy control subjects and in subjects who had bronchiectasis and recurrent bronchial infection with this bacterium. Cells were stimulated with live H. influenzae and intracellular cytokine production and release of cytotoxic granules measured. Control subjects had significantly higher levels of interferon gamma production by both CTL and NK cells, while levels of cytotoxic granule release were similar in both groups. The main lymphocyte subsets that proliferated in response to H. influenzae stimulation were the CTL and NK cells. The results suggest that CTL and NK cell responses may be important in preventing disease from nontypeable H. influenzae infection.

Assessing immune function in adult bronchiectasis.

Bronchiectasis is characterized by chronic airway infection and damage and remains an important health problem. Recent literature has emphasized the role of host defence and immune deficiency in the pathogenesis of bronchiectasis, but there have been few studies of immune function in adult bronchiectasis. A comprehensive screen of immune function was conducted in 103 adult patients with bronchiectasis, encompassing full blood examinations, immunoglobulins and IgG isotypes, complement levels, lymphocyte subsets and neutrophil function. Full blood examinations were normal in this cohort, as were complement levels. Statistical analysis confirmed that a significant number of subjects had low levels of IgG3 (13 patients), B cell lymphocytes (six patients) and T helper cell lymphocytes (seven patients) when compared with controls (P<0.05). The most common abnormality was found with testing of the neutrophil oxidative burst. All subjects had a normal neutrophil phagocytic function but 33 of the subjects had an oxidative burst that was below the normal range (P<0001). Almost half the group (45 subjects) had abnormally low levels of one of these four parameters. The findings of low B cells, Th cells and oxidative burst in bronchiectasis are novel. The results emphasize the importance of immune function assessment for adult bronchiectasis.

Extracorporeal membrane oxygenation in pregnancy.

We describe the use of extracorporeal membrane oxygenation in pregnancy. There were no major complications, and the outcome was successful for mother and baby.

An Australian isolate of Mycobacterium shimoidei.

A case of Mycobacterium shimoidei in a 75 year old man is reported. He had been a smoker, with a past history of bullous emphysema and a lung abscess. He had a 12 month history of weight loss, night sweats, with increased cough and sputum, and progressive opacification of the left apex with cavity formation. Sputum repeatedly grew M. shimoidei, identification of which was confirmed with high-pressure liquid chromatography (HPLC). He was treated for 45 days with three drugs to which the organism was sensitive, but failed to respond. His death was attributed to mycobacterial infection.

Chronic persistent cough: use of ipratropium bromide in undiagnosed cases following upper respiratory tract infection.

The clinical effects of inhaled ipratropium bromide were studied in 14 non-smoking patients with persistent post-viral infective cough employing a controlled double-blind, cross-over trial. Patients were selected if they demonstrated no apparent underlying cause for their persistent cough after appropriate radiological and respiratory function tests including methacholine reactivity and bronchoscopic examination. Inhaled ipratropium bromide (320 micrograms day-1) produced significantly less day and night time cough (P < 0.05) with overall clinical improvement in 12 cases, five of whom had total resolution of their cough. We conclude that ipratropium bromide is an effective treatment in non-smoking adults with protracted cough following clinical upper respiratory tract infection.

Leucogyrophana pinastri, a wood decay fungus as a probable cause of an extrinsic allergic alveolitis syndrome.

Two patients were suspected of having extrinsic allergic alveolitis due to exposure to an agent in their home environment. On inspection of their houses, fungal decay was evident in the floorboards, and fungal spores were found deposited on many surfaces. The decay fungus was later identified as Leucogyrophana pinastri. Using an extract of the fruiting bodies and mycelium of this fungus, precipitating antibodies were identified in the sera of both patients. Based on the known exposure by the two patients to these small spores, the absence of a likely alternative allergen, the similarity between these two cases, and the positive precipitin test results, L. pinastri was considered to be the most likely cause of extrinsic allergic alveolitis in our cases.

Intrathoracic manifestations of disseminated prostatic adenocarcinoma.

Four cases of disseminated adenocarcinoma of the prostate illustrating the clinical spectrum of intrathoracic involvement in this disease are presented. In two cases the presenting features of prostatic cancer were with lymphangitis carcinomatosa and an isolated pleural effusion, whereas two other cases developed intrathoracic metastases in the setting of previously known locally advanced prostatic cancer. In one this took the form of hilar and mediastinal lymphadenopathy and in the other that of pulmonary nodules. An immuno-cytochemical marker for prostatic specific antigen, a highly sensitive and specific tool for identifying prostatic epithelium, identified the prostate as the primary site of malignancy in the first two cases. Symptomatic and radiological responses were noted in all four cases after bilateral orchidectomy. Pulmonary metastases are common in the advanced stages of prostatic cancer but may also be present at the initial presentation with the disease even when the primary tumour is not clinically apparent. We recommend that (i) immuno-cytochemical stains for prostatic specific antigen are applied to all lung, pleural and mediastinal biopsy specimens showing adenocarcinoma in male patients, and (ii) all males with intrathoracic adenocarcinoma have prostatic aspiration cytology performed if the prostatic specific antigen stain is positive.

The role of bronchoalveolar lavage in the diagnosis of suspected opportunistic pneumonia.

We report 50 immunocompromised patients with pulmonary infiltrates who underwent fibreoptic bronchoscopy, including bronchoalveolar lavage, on 56 occasions. The underlying diseases were mostly lymphoma, leukemia, other malignancies and renal failure. The commonest immunodeficiency factors were chemotherapy, steroids and neutropenia. A positive diagnosis could be made from analysis of the bronchoalveolar lavage on 59% (33/56) occasions. This was a comparable yield to transbronchial lung biopsy 57% (16/27), and superior to proximal airways wash 24% (13/55), or bronchial brushings 29% (10/34). Open lung biopsy added additional diagnostic information in three of the four cases in which it was performed. The most common final diagnoses were bacterial, viral or Pneumocystis carinii pneumonia and recurrent malignancy. We conclude that bronchoalveolar lavage is a safe procedure with a high diagnostic yield in the immunocompromised host with suspected opportunistic pneumonia.

Use of ipratropium bromide in patients with severe airways obstruction.

In ten adult patients with severe, partially reversible airflow obstruction due to asthma, with or without co-existent chronic bronchitis, the acute bronchodilator responses of ipratropium bromide (40 micrograms) and terbutaline (500 micrograms) from metered-dose inhalers, atropine methonitrate (2 mg) as a wet aerosol and placebo were compared in a double blind trial. Also the combination of ipratropium bromide and terbutaline aerosols was compared with both ipratropium and terbutaline alone in short-term and long-term studies. In the short-term study, all the drugs produced significant bronchodilatation compared with placebo. The responses to ipratropium bromide and terbutaline alone were not significantly different. The combination of ipratropium bromide with terbutaline did not produce significantly greater changes in the FEV1, SGaw or static lung volume than terbutaline alone. Atropine methonitrate however, produced significantly greater changes of the airway conductance (SGaw) and static lung volumes (TLC and RV) but not FEV1, when compared to ipratropium bromide. When administered over randomised periods of one month each there were no significant differences between the combination of ipratropium bromide and terbutaline and each drug alone in daily airflometer recordings, daily symptom scores or fortnightly spirometry and clinical assessment. It is concluded that ipratropium bromide, in the conventional dose of 40 microgramm by metered-dose inhaler produces safe, effective bronchodilatation. Its effect, however, did not significantly augment that of the beta adrenergic stimulant, terbutaline and was less than that of atropine methonitrate 2 mg by wet aerosol.

Transfer of matching performance in pigeons.

Three pigeons were given extensive training on three-key simultaneous matching problems using geometric-form and hue stimuli. After acquisition of matching, the birds were tested with pairs of stimuli involving one or both novel members. Matching during the test stimuli occurred less often than during the later stages of the acquisition phase, but more often than would occur if no transfer had taken place. Greater positive transfer was observed for problems that involved one, rather than two, novel stimuli. In the second phase of the experiment, previously trained birds were shifted to problems that required symbolic matching, i.e., the pigeons had to associate a particular center-key stimulus with a particular side-key stimulus. On each trial, one of two simuli was presented on the center key, and two other stimuli, different from those used on the center key, were displayed on the side keys. When the problem shift was introduced, correct responding was impaired, but remained considerably above chance level and quickly recovered in following sessions. The results were interpreted as favoring a stimulus-response-chaining account of matching behavior.

Acute changes of lung volumes and lung mechanics in asthma and in normal subjects.

Lung volumes, pulmonary mechanics, and specific airway conductance (sGaw) were studied before and 15 minutes after 200 microgram of aerosol salbutamol in nine asthmatics undergoing mild spontaneous exacerbations of their disease and in five normal subjects. In addition, three of the normal subjects were studied after voluntarily breathing at high lung volumes for one minute. The normal subjects and four of the asthmatics showed no overall changes in lung volumes or pressure-volume (PV) curves after salbutamol, even though airway dilatation was produced in the asthmatic subjects. In another five asthmatics, salbutamol induced a significant fall in the total lung capacity (TLC) in three, and in the residual volume and functional residual capacity in all five. There was a significant displacement of the PV curve downwards and to the right in all five, with increased lung compliance (Cl stat) in two. The fall in TLC could be accounted for by the increase in lung elasticity. There is reason to believe that this change in lung mechanics could be due to the reversal of asthma-induced stress relaxation. Sustained breathing at high lung volume is known to cause stress relaxation of the lung. However, this breathing pattern did not alter the PV curve or TLC in two of three normal subjects, which is consistent with stress relaxation being rapidly reversible. The other normal subject had an acute shift of the PV curve upwards and to the left after breathing at high lung volume. It has been concluded that stress relaxation is usually rapidly reversed but that in some individuals it may only be slowly reversed. This more persistent form of stress relaxation may contribute to the acute changes of TLC found in some asthmatics.