Markus Henke - Academia.edu (original) (raw)
Papers by Markus Henke
Deutsches Aerzteblatt Online
Pediatric Pulmonology, 2012
The clinically significant actions of oral azithromycin in modifying progressive cystic fibrosis ... more The clinically significant actions of oral azithromycin in modifying progressive cystic fibrosis (CF) lung disease have been well documented. In vitro and clinical data suggests that clarithromycin has immunomodulatory properties similar to other 14-member macrolides, however two previously reported short term, open label trials of clairthromycin in small numbers of patients with CF failed to show significant benefits in modifying lung function or inflammation. We performed an international double blind, cross-over trial in which 63 subjects with CF were studied while receiving either placeo or 500 mg oral clarithromycin twice daily for 5 months, with a 1-month wash-out. The primary efficacy end point was the change in lung function (FEV 1 and FVC) during the clarithromycin treatment period compared to placebo treatment. Secondary efficacy end points included; quality of life, number of pulmonary exacerbations, height and weight, sputum inflammatory mediator content, sputum transportability and surface properties, bacterial flora, nasal potential difference, and breath condensate. No significant difference in either the primary efficacy end point or any secondary end point was seen during the period of clarithromycin treatment compared to those seen during placebo administration. We conclude that clarithromycin is not effective in treating CF lung disease. Pediatr Pulmonol.
Journal of Clinical Microbiology, 2002
Beauveria spp. are ubiquitous fungal entomopathogens that are commercially distributed as biologi... more Beauveria spp. are ubiquitous fungal entomopathogens that are commercially distributed as biological insecticides worldwide. In this paper we describe the clinical manifestation, diagnosis, and therapy of the first documented human deep tissue infection with an entomopathogenic Beauveria species in a patient receiving immunosuppressive therapy and describe the morphological and molecular characterization of the mold.
AJP: Lung Cellular and Molecular Physiology, 2014
Hemeoxygenase-1 (HO-1), an inducible heat shock protein, is upregulated in response to multiple c... more Hemeoxygenase-1 (HO-1), an inducible heat shock protein, is upregulated in response to multiple cellular insults via oxidative stress, lipopolysaccharides (LPS), and hypoxia. In this study, we investigated in vitro the role of Toll-like receptor 4 (TLR4), hypoxia-inducible factor 1α (HIF-1α), and iron on HO-1 expression in cystic fibrosis (CF). Immunohistochemical analysis of TLR4, HO-1, ferritin, and HIF-1α were performed on lung sections of CFTR−/− and wild-type mice. CFBE41o- and 16HBE14o- cell lines were employed for in vitro analysis via immunoblotting, immunofluorescence, real-time PCR, luciferase reporter gene analysis, and iron quantification. We observed a reduced TLR4, HIF-1α, HO-1, and ferritin in CFBE41o- cell line and CF mice. Knockdown studies using TLR4-siRNA in 16HBE14o- revealed significant decrease of HO-1, confirming the role of TLR4 in HO-1 downregulation. Inhibition of HO-1 using tin protoporphyrin in 16HBE14o- cells resulted in increased iron levels, suggesting...
Journal of Clinical Anesthesia
To evaluate the incidence and impact on clinical outcome of complications observed during high-fr... more To evaluate the incidence and impact on clinical outcome of complications observed during high-frequency jet ventilation (HFJV) at interventional bronchoscopy and to identify the perioperative factors that may be associated to an increased incidence of such complications. Observational retrospective, study with an observational prospective validation of the statistically significant associations. University hospital. The retrospective study involved 276 patients who underwent an interventional rigid bronchoscopy during general anesthesia and HFJV. Forty consecutive patients were accrued for the prospective validation group. INTERVENTIONS/MEASUREMENTS: Information recorded included patient medical history and perioperative complications observed at HFJV-managed bronchoscopic procedures and their impact on clinical outcome until hospital discharge. At least one complication was detected in 38% of retrospective patients and 55% of prospective patients. Most frequent complications were hypercapnia, hypoxemia, and hemodynamic instability, but just one case of barotrauma in the retrospective group. Despite the high incidence, these complications were transient and did not increase hospital stay, whereas technical failure to widen airway lumen was associated with an adverse prognosis. Several clinical parameters showed a significant association with complications in the univariate analysis. However, the multivariate analysis only evidenced two independent predictive factors: the ASA physical status scale and baseline oxygen saturation. Classification in ASA physical status IV group and a baseline oxygen saturation of 95% or less independently predicted the development of complications during interventional rigid bronchoscopy with HFJV.
Herz
Dyspnea is one of the major clinical symptoms which patients report to general practitioners, int... more Dyspnea is one of the major clinical symptoms which patients report to general practitioners, internists, cardiologists and hospitals. In this review article we discuss the evidence of medical history, laboratory procedures and diagnostic investigations to approach patients with acute or chronic dyspnea and try to structure this complex symptom dyspnea to reach the etiology of the underlying disease.
Progress in Inflammation Research, 2005
Respiratory Research, 2015
Proteases have been shown to degrade airway mucin proteins and to damage the epithelium impairing... more Proteases have been shown to degrade airway mucin proteins and to damage the epithelium impairing mucociliary clearance. There are increased proteases in the COPD airway but changes in protease-antiprotease balance and mucin degradation have not been investigated during the course of a COPD exacerbation. We hypothesized that increased protease levels would lead to mucin degradation in acute COPD exacerbations. Methods: We measured neutrophil elastase (NE) and alpha 1 protease inhibitor (A1-PI) levels using immunoblotting, and conducted protease inhibitor studies, zymograms, elastin substrate assays and cigarette smoke condensate experiments to evaluate the stability of the gel-forming mucins, MUC5AC and MUC5B, before and 5-6 weeks after an acute pulmonary exacerbation of COPD (n = 9 subjects). Results: Unexpectedly, mucin concentration and mucin stability were highest at the start of the exacerbation and restored to baseline after 6 weeks. Consistent with these data, immunoblots and zymograms confirmed decreased NE concentration and activity and increased A1-PI at the start of the exacerbation. After recovery there was an increase in NE activity and a decrease in A1-PI levels. In vitro, protease inhibitor studies demonstrated that serine proteases played a key role in mucin degradation. Mucin stability was further enhanced upon treating with cigarette smoke condensate (CSC).
CHEST Journal, 2014
The term bronchial hyperresponsiveness is generally used to describe a heightened airway smooth m... more The term bronchial hyperresponsiveness is generally used to describe a heightened airway smooth muscle bronchoconstrictor response measured by bronchoprovocation testing. However, the airway also responds to infl ammation or bronchoprovocation with increased mucus secretion. We use the term "secretory hyperresponsiveness" to mean increased mucus secretion either intrinsically or in response to bronchoprovocation. This is not the same as retained phlegm or sputum. Unlike smooth muscle contraction, which is rapidly reversible using a bronchodilator, mucus hypersecretion produces airfl ow limitation that reverses more slowly and depends upon secretion clearance from the airway. Certain groups of patients appear to have greater mucus secretory response, including those with middle lobe syndrome, coughdominant ("cough-variant") asthma, and severe asthma. Secretory hyperresponsiveness also is a component of forms of lung cancer associated with bronchorrhea. An extreme form of secretory hyperresponsiveness may lead to plastic bronchitis, a disease characterized by rigid branching mucus casts that obstruct the airway. Secretory hyperresponsiveness and mucus hypersecretion appear to be related to activation of the extracellular-regulated kinase 1/2, signaling through the epidermal growth factor receptor, or secretory phospholipases A2. Recognizing secretory hyperresponsiveness as a distinct clinical entity may lead to more eff ective and targeted therapy for these diseases.
COPD: Journal of Chronic Obstructive Pulmonary Disease, 2005
It has been established that mucus hypersecretion and decreased mucus clearance contribute to the... more It has been established that mucus hypersecretion and decreased mucus clearance contribute to the morbidity of chronic obstructive pulmonary disease (COPD). Indeed, the classic definition of chronic bronchitis relies on determining the frequency and duration of sputum expectoration. Despite the well recognized importance of this symptom, there are few therapies routinely used to decrease the sputum production or to improve clearance. There are fewer well conducted clinical trials of existing medications and this has led many regulatory agencies, notably the Food and Drug Administration (FDA), to refuse to register these medications or approve their sale. Similarly, airway clearance devices and chest physical therapy have not been well studied in COPD. Carefully conducted studies of interventions to improve airway clearance, similar to those done in cystic fibrosis (CF), may help us to identify effective therapies and possibly novel diagnostic tests for the management of COPD.
Pharmacology and Therapeutics, 2008
Macrolide antibiotics administered in sub-antimicrobial doses improve pulmonary function and decr... more Macrolide antibiotics administered in sub-antimicrobial doses improve pulmonary function and decrease exacerbation frequency for persons with diffuse panbronchiolitis or cystic fibrosis. Data also suggest a beneficial effect of macrolide antibiotics in the treatment of steroid dependent asthma. Many potential immunomodulatory effects of macrolide antibiotics have been reported including the ability to down-regulate prolonged inflammation, decreasing airway mucus secretion, inhibiting bacterial biofilm, decreasing the production of reactive oxygen species, inhibiting neutrophil activation and mobilization, accelerating neutrophil apoptosis, and blocking the activation of nuclear transcription factors. Macrolides initially decrease, then increase, and have finally a sustained suppression of cytokine secretions from normal human bronchial epithelial cells through inhibition and activation of extracellular signal-regulated kinases (ERK) and then reversibly retard cell proliferation probably through ERK. Consistent with this, macrolide antibiotics possibly reduce mucin production as well as neutrophil migration by interfering with ERK signal transduction.
Respirology, 2010
Background and objective: The diagnostic yield from fluoroscopy-guided bronchoscopic transbronchi... more Background and objective: The diagnostic yield from fluoroscopy-guided bronchoscopic transbronchial biopsy of small solitary pulmonary nodules is low. The hypothesis tested in the present study was that the diagnostic yield can be significantly increased by combining flexible bronchoscopy with CT-guidance using a dedicated low-dose protocol. Methods: CT-guided transbronchial biopsies were performed in 15 patients with a newly diagnosed solitary peripheral pulmonary nodule and negative conventional bronchoscopic biopsies under fluoroscopic guidance. For imaging, a multi-detector helical CT unit, adjusted at 120 kV, 15 mAs/slice, 4 ¥ 5 mm collimation, 10 mm reconstructed slice thickness and a maximal scan length of 150 mm, was used. After advancing the biopsy forceps towards the lesion, a CT scan was obtained. When the tip of the forceps reached or penetrated the lesion a biopsy was taken, otherwise the procedure was repeated with a maximum of eight attempts. The effective radiation dose was calculated. Results: The average diameter of the nodules was 23 Ϯ 6 mm (mean Ϯ SD) with a maximum distance to the parietal pleura of 18 mm (mean 6.5 mm). A mean of 4.1 (range 2-8) CT scans was performed to localize the lesion. In four patients, the forceps only reached the periphery of the nodule. In one patient, the nodule was missed in all attempts. Histology was malignant in eight patients and benign in four patients. In three patients, biopsy results were false negative (benign or non-specific instead of malignant). The overall diagnostic yield was 73%. Complications consisted of two pneumothoraces, one of which necessitated a chest tube. Mean effective radiation dose was 0.55 mSv (range 0.3-1.0). Conclusions: CT-guided transbronchial biopsy can be a valuable diagnostic tool in evaluating solitary pulmonary nodules. This applies for selected patients when other diagnostic methods are either unavailable or inappropriate. The diagnostic yield is high and, when a low-dose protocol is used, radiation exposure can be kept at a minimum.
Journal of Cystic Fibrosis, 2009
The aim of this study was to determine the prevalence of different autoantibodies (aAbs) in adult... more The aim of this study was to determine the prevalence of different autoantibodies (aAbs) in adult French cystic fibrosis (CF) patients and to look for a correlation between autoimmunity, patient characteristics and survival. Methods: The sera of 144 patients were screened for a wide range of Abs. Clinical, biological and bacteriological characteristics and CFTR genotype were recorded and progression of lung disease was examined. Results: One hundred and thirteen patients (78.5%) displayed one or several aAbs, predominantly IgA anti-Saccharomyces cerevisiae antibodies (ASCA IgA) (43.7%) and anti-neutrophil cytoplasmic antibodies (ANCA) (40%), of which 59% showed bactericidal/permeability-increasing protein (BPI) specificity. The presence of BPI-ANCA was associated with the number of antibiotic courses, low body mass index, P aeruginosa colonisation, presence of resistant P aeruginosa, low FEV1, CFrelated liver disease, hypergammaglobulinaemia, male gender and inflammatory syndrome. The presence of ASCA IgA was correlated with male gender and hypergammaglobulinaemia. Forty-one patients presented chronic respiratory failure and/or requested lung transplantation or died during follow-up. These events were more frequent in patients with BPI-ANCA or ASCA IgA. Conclusion: These findings confirmed the high frequency of aAbs in CF, particularly BPI-ANCA and ASCA IgA, and the link between BPI-ANCA, severity of lung disease and CF prognosis.
Deutsches Aerzteblatt Online
Pediatric Pulmonology, 2012
The clinically significant actions of oral azithromycin in modifying progressive cystic fibrosis ... more The clinically significant actions of oral azithromycin in modifying progressive cystic fibrosis (CF) lung disease have been well documented. In vitro and clinical data suggests that clarithromycin has immunomodulatory properties similar to other 14-member macrolides, however two previously reported short term, open label trials of clairthromycin in small numbers of patients with CF failed to show significant benefits in modifying lung function or inflammation. We performed an international double blind, cross-over trial in which 63 subjects with CF were studied while receiving either placeo or 500 mg oral clarithromycin twice daily for 5 months, with a 1-month wash-out. The primary efficacy end point was the change in lung function (FEV 1 and FVC) during the clarithromycin treatment period compared to placebo treatment. Secondary efficacy end points included; quality of life, number of pulmonary exacerbations, height and weight, sputum inflammatory mediator content, sputum transportability and surface properties, bacterial flora, nasal potential difference, and breath condensate. No significant difference in either the primary efficacy end point or any secondary end point was seen during the period of clarithromycin treatment compared to those seen during placebo administration. We conclude that clarithromycin is not effective in treating CF lung disease. Pediatr Pulmonol.
Journal of Clinical Microbiology, 2002
Beauveria spp. are ubiquitous fungal entomopathogens that are commercially distributed as biologi... more Beauveria spp. are ubiquitous fungal entomopathogens that are commercially distributed as biological insecticides worldwide. In this paper we describe the clinical manifestation, diagnosis, and therapy of the first documented human deep tissue infection with an entomopathogenic Beauveria species in a patient receiving immunosuppressive therapy and describe the morphological and molecular characterization of the mold.
AJP: Lung Cellular and Molecular Physiology, 2014
Hemeoxygenase-1 (HO-1), an inducible heat shock protein, is upregulated in response to multiple c... more Hemeoxygenase-1 (HO-1), an inducible heat shock protein, is upregulated in response to multiple cellular insults via oxidative stress, lipopolysaccharides (LPS), and hypoxia. In this study, we investigated in vitro the role of Toll-like receptor 4 (TLR4), hypoxia-inducible factor 1α (HIF-1α), and iron on HO-1 expression in cystic fibrosis (CF). Immunohistochemical analysis of TLR4, HO-1, ferritin, and HIF-1α were performed on lung sections of CFTR−/− and wild-type mice. CFBE41o- and 16HBE14o- cell lines were employed for in vitro analysis via immunoblotting, immunofluorescence, real-time PCR, luciferase reporter gene analysis, and iron quantification. We observed a reduced TLR4, HIF-1α, HO-1, and ferritin in CFBE41o- cell line and CF mice. Knockdown studies using TLR4-siRNA in 16HBE14o- revealed significant decrease of HO-1, confirming the role of TLR4 in HO-1 downregulation. Inhibition of HO-1 using tin protoporphyrin in 16HBE14o- cells resulted in increased iron levels, suggesting...
Journal of Clinical Anesthesia
To evaluate the incidence and impact on clinical outcome of complications observed during high-fr... more To evaluate the incidence and impact on clinical outcome of complications observed during high-frequency jet ventilation (HFJV) at interventional bronchoscopy and to identify the perioperative factors that may be associated to an increased incidence of such complications. Observational retrospective, study with an observational prospective validation of the statistically significant associations. University hospital. The retrospective study involved 276 patients who underwent an interventional rigid bronchoscopy during general anesthesia and HFJV. Forty consecutive patients were accrued for the prospective validation group. INTERVENTIONS/MEASUREMENTS: Information recorded included patient medical history and perioperative complications observed at HFJV-managed bronchoscopic procedures and their impact on clinical outcome until hospital discharge. At least one complication was detected in 38% of retrospective patients and 55% of prospective patients. Most frequent complications were hypercapnia, hypoxemia, and hemodynamic instability, but just one case of barotrauma in the retrospective group. Despite the high incidence, these complications were transient and did not increase hospital stay, whereas technical failure to widen airway lumen was associated with an adverse prognosis. Several clinical parameters showed a significant association with complications in the univariate analysis. However, the multivariate analysis only evidenced two independent predictive factors: the ASA physical status scale and baseline oxygen saturation. Classification in ASA physical status IV group and a baseline oxygen saturation of 95% or less independently predicted the development of complications during interventional rigid bronchoscopy with HFJV.
Herz
Dyspnea is one of the major clinical symptoms which patients report to general practitioners, int... more Dyspnea is one of the major clinical symptoms which patients report to general practitioners, internists, cardiologists and hospitals. In this review article we discuss the evidence of medical history, laboratory procedures and diagnostic investigations to approach patients with acute or chronic dyspnea and try to structure this complex symptom dyspnea to reach the etiology of the underlying disease.
Progress in Inflammation Research, 2005
Respiratory Research, 2015
Proteases have been shown to degrade airway mucin proteins and to damage the epithelium impairing... more Proteases have been shown to degrade airway mucin proteins and to damage the epithelium impairing mucociliary clearance. There are increased proteases in the COPD airway but changes in protease-antiprotease balance and mucin degradation have not been investigated during the course of a COPD exacerbation. We hypothesized that increased protease levels would lead to mucin degradation in acute COPD exacerbations. Methods: We measured neutrophil elastase (NE) and alpha 1 protease inhibitor (A1-PI) levels using immunoblotting, and conducted protease inhibitor studies, zymograms, elastin substrate assays and cigarette smoke condensate experiments to evaluate the stability of the gel-forming mucins, MUC5AC and MUC5B, before and 5-6 weeks after an acute pulmonary exacerbation of COPD (n = 9 subjects). Results: Unexpectedly, mucin concentration and mucin stability were highest at the start of the exacerbation and restored to baseline after 6 weeks. Consistent with these data, immunoblots and zymograms confirmed decreased NE concentration and activity and increased A1-PI at the start of the exacerbation. After recovery there was an increase in NE activity and a decrease in A1-PI levels. In vitro, protease inhibitor studies demonstrated that serine proteases played a key role in mucin degradation. Mucin stability was further enhanced upon treating with cigarette smoke condensate (CSC).
CHEST Journal, 2014
The term bronchial hyperresponsiveness is generally used to describe a heightened airway smooth m... more The term bronchial hyperresponsiveness is generally used to describe a heightened airway smooth muscle bronchoconstrictor response measured by bronchoprovocation testing. However, the airway also responds to infl ammation or bronchoprovocation with increased mucus secretion. We use the term "secretory hyperresponsiveness" to mean increased mucus secretion either intrinsically or in response to bronchoprovocation. This is not the same as retained phlegm or sputum. Unlike smooth muscle contraction, which is rapidly reversible using a bronchodilator, mucus hypersecretion produces airfl ow limitation that reverses more slowly and depends upon secretion clearance from the airway. Certain groups of patients appear to have greater mucus secretory response, including those with middle lobe syndrome, coughdominant ("cough-variant") asthma, and severe asthma. Secretory hyperresponsiveness also is a component of forms of lung cancer associated with bronchorrhea. An extreme form of secretory hyperresponsiveness may lead to plastic bronchitis, a disease characterized by rigid branching mucus casts that obstruct the airway. Secretory hyperresponsiveness and mucus hypersecretion appear to be related to activation of the extracellular-regulated kinase 1/2, signaling through the epidermal growth factor receptor, or secretory phospholipases A2. Recognizing secretory hyperresponsiveness as a distinct clinical entity may lead to more eff ective and targeted therapy for these diseases.
COPD: Journal of Chronic Obstructive Pulmonary Disease, 2005
It has been established that mucus hypersecretion and decreased mucus clearance contribute to the... more It has been established that mucus hypersecretion and decreased mucus clearance contribute to the morbidity of chronic obstructive pulmonary disease (COPD). Indeed, the classic definition of chronic bronchitis relies on determining the frequency and duration of sputum expectoration. Despite the well recognized importance of this symptom, there are few therapies routinely used to decrease the sputum production or to improve clearance. There are fewer well conducted clinical trials of existing medications and this has led many regulatory agencies, notably the Food and Drug Administration (FDA), to refuse to register these medications or approve their sale. Similarly, airway clearance devices and chest physical therapy have not been well studied in COPD. Carefully conducted studies of interventions to improve airway clearance, similar to those done in cystic fibrosis (CF), may help us to identify effective therapies and possibly novel diagnostic tests for the management of COPD.
Pharmacology and Therapeutics, 2008
Macrolide antibiotics administered in sub-antimicrobial doses improve pulmonary function and decr... more Macrolide antibiotics administered in sub-antimicrobial doses improve pulmonary function and decrease exacerbation frequency for persons with diffuse panbronchiolitis or cystic fibrosis. Data also suggest a beneficial effect of macrolide antibiotics in the treatment of steroid dependent asthma. Many potential immunomodulatory effects of macrolide antibiotics have been reported including the ability to down-regulate prolonged inflammation, decreasing airway mucus secretion, inhibiting bacterial biofilm, decreasing the production of reactive oxygen species, inhibiting neutrophil activation and mobilization, accelerating neutrophil apoptosis, and blocking the activation of nuclear transcription factors. Macrolides initially decrease, then increase, and have finally a sustained suppression of cytokine secretions from normal human bronchial epithelial cells through inhibition and activation of extracellular signal-regulated kinases (ERK) and then reversibly retard cell proliferation probably through ERK. Consistent with this, macrolide antibiotics possibly reduce mucin production as well as neutrophil migration by interfering with ERK signal transduction.
Respirology, 2010
Background and objective: The diagnostic yield from fluoroscopy-guided bronchoscopic transbronchi... more Background and objective: The diagnostic yield from fluoroscopy-guided bronchoscopic transbronchial biopsy of small solitary pulmonary nodules is low. The hypothesis tested in the present study was that the diagnostic yield can be significantly increased by combining flexible bronchoscopy with CT-guidance using a dedicated low-dose protocol. Methods: CT-guided transbronchial biopsies were performed in 15 patients with a newly diagnosed solitary peripheral pulmonary nodule and negative conventional bronchoscopic biopsies under fluoroscopic guidance. For imaging, a multi-detector helical CT unit, adjusted at 120 kV, 15 mAs/slice, 4 ¥ 5 mm collimation, 10 mm reconstructed slice thickness and a maximal scan length of 150 mm, was used. After advancing the biopsy forceps towards the lesion, a CT scan was obtained. When the tip of the forceps reached or penetrated the lesion a biopsy was taken, otherwise the procedure was repeated with a maximum of eight attempts. The effective radiation dose was calculated. Results: The average diameter of the nodules was 23 Ϯ 6 mm (mean Ϯ SD) with a maximum distance to the parietal pleura of 18 mm (mean 6.5 mm). A mean of 4.1 (range 2-8) CT scans was performed to localize the lesion. In four patients, the forceps only reached the periphery of the nodule. In one patient, the nodule was missed in all attempts. Histology was malignant in eight patients and benign in four patients. In three patients, biopsy results were false negative (benign or non-specific instead of malignant). The overall diagnostic yield was 73%. Complications consisted of two pneumothoraces, one of which necessitated a chest tube. Mean effective radiation dose was 0.55 mSv (range 0.3-1.0). Conclusions: CT-guided transbronchial biopsy can be a valuable diagnostic tool in evaluating solitary pulmonary nodules. This applies for selected patients when other diagnostic methods are either unavailable or inappropriate. The diagnostic yield is high and, when a low-dose protocol is used, radiation exposure can be kept at a minimum.
Journal of Cystic Fibrosis, 2009
The aim of this study was to determine the prevalence of different autoantibodies (aAbs) in adult... more The aim of this study was to determine the prevalence of different autoantibodies (aAbs) in adult French cystic fibrosis (CF) patients and to look for a correlation between autoimmunity, patient characteristics and survival. Methods: The sera of 144 patients were screened for a wide range of Abs. Clinical, biological and bacteriological characteristics and CFTR genotype were recorded and progression of lung disease was examined. Results: One hundred and thirteen patients (78.5%) displayed one or several aAbs, predominantly IgA anti-Saccharomyces cerevisiae antibodies (ASCA IgA) (43.7%) and anti-neutrophil cytoplasmic antibodies (ANCA) (40%), of which 59% showed bactericidal/permeability-increasing protein (BPI) specificity. The presence of BPI-ANCA was associated with the number of antibiotic courses, low body mass index, P aeruginosa colonisation, presence of resistant P aeruginosa, low FEV1, CFrelated liver disease, hypergammaglobulinaemia, male gender and inflammatory syndrome. The presence of ASCA IgA was correlated with male gender and hypergammaglobulinaemia. Forty-one patients presented chronic respiratory failure and/or requested lung transplantation or died during follow-up. These events were more frequent in patients with BPI-ANCA or ASCA IgA. Conclusion: These findings confirmed the high frequency of aAbs in CF, particularly BPI-ANCA and ASCA IgA, and the link between BPI-ANCA, severity of lung disease and CF prognosis.