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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. © 2008 British Society for Immunology.

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. © 2008 British Society for Immunology.

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. © 2006 British Society for Immunology.

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 mug 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.

Background: There is little information available on the features of initial presentation of bronchiectasis and documentation of the onset and progress of symptoms leading up to this. Therefore a study was performed on a large cohort of adult patients presenting to Monash Medical Centre (MMC) to survey the course of their disease up to the time of diagnosis. Objective(s): To characterise the onset and presenting clinical features of bronchiectasis in adults. Method(s): A cross-sectional study of 103 adults presenting to a tertiary referral hospital with newly diagnosed bronchiectasis. Clinical features of bronchiectasis and results of spirometry, sputum microbiology and radiology were assessed and correlated. Result(s): Most patients had idiopathic bronchiectasis (74%) and did not have other significant disease. The dominant symptom was chronic productive cough present in 98% of patients with other important symptoms being chronic rhinosinusitis (70%), dyspnoea (62%), and fatigue (74%). Most patients had had a chronic productive cough for over 30 years prior to diagnosis and over 80% of patients had chronic respiratory symptoms from childhood. The dominant finding on physical examination was the presence of crackles which were generally bi-basal. Spirometry showed mild airway obstruction with an average forced expiratory volume in 1 s of the cohort of 76% predicted. Radiologic imaging generally showed multilobar disease (80%). Conclusion(s): The typical profile of bronchiectasis in this group of patients was of longstanding productive cough, rhinosinusitis and fatigue in non-smokers with crackles on chest auscultation. © 2006 Elsevier Ltd. All rights reserved.

We describe a series of 4 subjects with markedly raised immunoglobulin E levels in association with idiopathic bronchiectasis. This has not been described previously and appears to be a distinct entity from other conditions such as allergic bronchopulmonary aspergillosis. © 2008 Elsevier Ltd. All rights reserved.

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. © 2008 British Society for Immunology.

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. © 2006 British Society for Immunology.

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 mug 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.

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. © 2008 British Society for Immunology.

Background: There is little information available on the features of initial presentation of bronchiectasis and documentation of the onset and progress of symptoms leading up to this. Therefore a study was performed on a large cohort of adult patients presenting to Monash Medical Centre (MMC) to survey the course of their disease up to the time of diagnosis. Objective(s): To characterise the onset and presenting clinical features of bronchiectasis in adults. Method(s): A cross-sectional study of 103 adults presenting to a tertiary referral hospital with newly diagnosed bronchiectasis. Clinical features of bronchiectasis and results of spirometry, sputum microbiology and radiology were assessed and correlated. Result(s): Most patients had idiopathic bronchiectasis (74%) and did not have other significant disease. The dominant symptom was chronic productive cough present in 98% of patients with other important symptoms being chronic rhinosinusitis (70%), dyspnoea (62%), and fatigue (74%). Most patients had had a chronic productive cough for over 30 years prior to diagnosis and over 80% of patients had chronic respiratory symptoms from childhood. The dominant finding on physical examination was the presence of crackles which were generally bi-basal. Spirometry showed mild airway obstruction with an average forced expiratory volume in 1 s of the cohort of 76% predicted. Radiologic imaging generally showed multilobar disease (80%). Conclusion(s): The typical profile of bronchiectasis in this group of patients was of longstanding productive cough, rhinosinusitis and fatigue in non-smokers with crackles on chest auscultation. © 2006 Elsevier Ltd. All rights reserved.

There is minimal published longitudinal data about pathogenic microorganisms in adults with bronchiectasis. Therefore a study was undertaken to assess the microbiologic profile over time in bronchiectasis. A prospective study of clinical and microbiologic outcomes was performed. Subjects were assessed by a respiratory physician and sputum sample were collected for analysis. Subjects were followed up and had repeat assessment performed. Eighty-nine subjects were followed up for a period of 5.7+/-3.6 years. On initial assessment the two most common pathogens isolated were Haemophilus influenzae (47%) and Pseudomonas aeruginosa (12%) whilst 21% had no pathogens isolated. On follow-up review results were similar (40% H. influenzae, 18% P. aeruginosa and 26% no pathogens). The prevalence of antibiotic resistance of isolates increased from 13% to 30%. Analysis of a series of H. influenzae isolates showed they were nearly all nontypeable and all were different subtypes. Subjects with no pathogens isolated from their sputum had the mildest disease, while subjects with P. aeruginosa had the most severe bronchiectasis. Many subjects with bronchiectasis are colonized with the same bacterium over an average follow-up of 5 years. Different pathogens are associated with different patterns of clinical disease. © 2007 Elsevier Ltd. All rights reserved.

We describe a series of 4 subjects with markedly raised immunoglobulin E levels in association with idiopathic bronchiectasis. This has not been described previously and appears to be a distinct entity from other conditions such as allergic bronchopulmonary aspergillosis. © 2008 Elsevier Ltd. All rights reserved.

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

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