A Rare Case of Primary Intrapulmonary Neurilemmoma Diagnosed in a 43-Year-Old Asymptomatic Man with a Well-defined Intrapulmonary Mass.

Neurilemmoma (NL), also termed schwannoma, presents as a well-circumscribed and encapsulated mass in the human body and is almost always solitary. CT scan of a patient with NL shows a round, ovoid, or lobulated well-demarcated solid mass of soft tissue density. Primary intrathoracic neurogenic tumors location varies. However, the development of such tumors is by far more common in the costovertebral angle of the posterior mediastinum. Here, we report a rare case of a 43-year-old patient, never smoker and previously healthy, who presented with a mass adjacent to the right pulmonary hilum. This was an incidental finding on a chest X-ray after annual checkup at his workplace. The diagnosis was primary intrapulmonary NL. Primary intrapulmonary NL is an extremely rare tumor. However, based on the above, chest CT findings of a well-defined solid mass in an asymptomatic patient should raise the suspicion of NL, irrespective of the tumor localization.

Investigation of bronchiectasis in severe uncontrolled asthma.

INTRODUCTION: The presence of bronchiectasis in patients with asthma varies in different reports, while a clear aetiological relation has not been precisely established. OBJECTIVES: To investigate the presence of bronchiectasis in patients with severe uncontrolled asthma and examine whether they contribute to the severity of asthma. METHODS: Patients with severe asthma were prospectively recruited. HRCT of the chest was performed to identify and grade bronchiectasis using the 'Smith' radiology scale. Investigation of the underlying cause was carried out for patients with bronchiectasis in order to exclude aetiologies other than asthma. The Statistical Package for the Social Sciences (SPSS), version 21, was used. RESULTS: Forty patients were studied, 28 women, mean age (±SD) 57.9 years (±12.4). Mean ACT score was 14.2(±4.9). Main symptoms were: wheezing (95%), cough (92%), dysponea (92%) and sputum production (72%). Mean duration of asthma was 16.5(±11.5) years, exacerbations: 4.4(±2.7)/year. In 27 patients (67.5%) bronchiectasis was diagnosed. In nine patients (22.5%) pathogens were cultured in sputum (mainly Pseudomonas aeruginosa, Haemophilus influenzae). Patients with sputum production and pathogens in sputum cultures had a higher Smith score compared to those without expectoration and without pathogens, respectively (P = .005, P < .0001). No correlation was found between the extent of bronchiectasis and lung function. The radiological severity of bronchiectasis was correlated with the antibiotic courses/year (P = .002). CONCLUSION: Bronchiectasis is common in patients with severe asthma. Sputum production and pathogen isolation in sputum may indicate the presence of bronchiectasis which seems to contribute to the severity of asthma.

Non CF-bronchiectasis: Aetiologic approach, clinical, radiological, microbiological and functional profile in 277 patients.

BACKGROUND AND OBJECTIVES: Non-Cystic Fibrosis (CF) bronchiectasis is common in Greece but little attention has been paid to the investigation of its aetiology, clinical, radiological, microbiological and lung function profile. METHODS: We prospectively evaluated patients with non-CF bronchiectasis confirmed by high resolution computed tomography (HRCT) of the chest. Aetiology, clinical data, radiology score, microbiological profile and lung function were investigated. RESULTS: We evaluated 277 patients (170 women) with bronchiectasis (mean age: 60.5 ± 16 years), 64% of them being non-smokers. Post-infectious (25.2%) and past tuberculosis (TB) (22.3%) were the most commonly identified underlying conditions, while no cause was found in 34% of the patients. The main symptoms were cough (82%), mucopurulent sputum (80%), dyspnea (60%) and haemoptysis (37%). Mean duration of symptoms was 9.7 (SD 10.7) years. Infectious exacerbations were observed in 67.5% of the patients with a mean frequency of 2.3 (SD 1.4) per year. The most frequent lung function pattern was the obstructive (43.1%) while 38% of the patients had normal spirometry. Pseudomonas aeruginosa was the most common pathogen yielded in sputum cultures (43%) followed by Haemophilus influenzae (12.6%). Patients with P. aeruginosa had a more long-standing disease and worse lung function. Radiological severity of the disease was mainly related to impaired lung function, P. aeruginosa isolation in sputum and frequent exacerbations. CONCLUSION: Data indicate that in Greece, "past" tuberculosis remains an important cause of bronchiectasis. P. aeruginosa was the predominant pathogen in the airways, associated with disease severity, while the most common lung function impairment was obstruction.

Survival in Idiopathic pulmonary fibrosis acute exacerbations: the non-steroid approach.

BACKGROUND: Idiopathic pulmonary fibrosis acute exacerbation (IPF-AE) constitutes IPF's most devastating event, representing the unexpected superimposition of diffuse alveolar damage of unknown etiology. Guidelines recommend high-dose steroids treatment despite unproven benefit. We hypothesized that previous immunosuppression and the administration of high-dose steroids adversely affect IPF-AE outcome. METHODS: We studied all consecutive patients hospitalized in our department for IPF deterioration from 2007 to June 2013. Our protocol consisted of immediate cessation of immunosuppression (if any), best supportive care, broad-spectrum antimicrobials and thorough evaluation to detect reversible causes of deterioration. Patients were followed-up for survival; post-discharge none received immunosuppression. RESULTS: Twenty-four out of 85 admissions (28%) fulfilled IPF-AE criteria. IPF-AE were analyzed both as unique events and as unique patients. As unique events 50% survived; 3 out of 12 (25%) in the group previously treated with immunosuppression whereas nine out of 12 (75%) in the group not receiving immunosuppression (p = 0.041). As unique patients 35.3% survived; 3 out of 6 (50%) in the never treated group whereas three out of 11 (27.3%) in the group receiving immunosuppression (p = 0.685). The history of immunosuppression significantly and adversely influenced survival (p = 0.035). Survival was greater in the never treated group compared to the immunosuppressed patients (p = 0.022). Post-discharge, our IPF-AE survivors had an 83% 1-year survival. CONCLUSIONS: By applying the above mentioned protocol half of our patients survived. The history of immunosuppression before IPF-AE adversely influences survival. Avoiding steroids in IPF patients may favor the natural history of the disease even at the moment of its most devastating event.

A 44-Year-Old Man With Chronic Cough, Weakness, and a Mediastinum Mass.

A 44-year-old white man presented with a 3-month history of dry cough and weakness. He had already been treated with antibiotics without any relief. He did not report dyspnea, fever, or expectoration. The patient's medical history was significant for mild arterial hypertension and autoimmune thyroiditis with normal thyroid hormone levels. He was a nonsmoker and had been in excellent health until symptom onset.

Pulmonary alveolar proteinosis: time to shift?

Pulmonary alveolar proteinosis (PAP) is categorized into hereditary, secondary and autoimmune PAP (aPAP) types. The common pathogenesis is the ability of the alveolar macrophages to catabolize phagocytized surfactant is affected. Hereditary PAP is caused by mutations involving the GM-CSF signaling, particularly in genes for the GM-CSF receptor and sometimes by GATA2 mutations. Secondary PAP occurs in hematologic malignancies, other hematologic disorders, miscellaneous malignancies, fume and dust inhalation, drugs, autoimmune disorders and immunodeficiencies. aPAP is related to the production of GM-CSF autoantibodies. PAP is characterized morphologically by the inappropriate and progressive 'occupation' of the alveolar spaces by an excessive amount of unprocessed surfactant, limiting gas exchange and gradually exhausting the respiratory reserve. Myeloid cells' immunity deteriorates, increasing the risk of infections. Treatment of PAP is based on its etiology. In aPAP, recent therapeutic advances might shift the treatment option from the whole lung lavage procedure under general anesthesia to the inhalation of GM-CSF 'as needed'.

Long-term inhaled granulocyte macrophage-colony-stimulating factor in autoimmune pulmonary alveolar proteinosis: effectiveness, safety, and lowest effective dose.

BACKGROUND AND OBJECTIVES: Granulocyte macrophage-colony-stimulating factor (GM-CSF) causes variable improvement in autoimmune pulmonary alveolar proteinosis (aPAP). Upon response to short-term treatment, patients are divided into responders and non-responders. The aim of this study was to test the hypothesis that long-term inhaled GM-CSF (iGM-CSF) is effective in all patients and that attainment of remission permits gradual de-escalation of the dose to the lowest effective safe dose. METHODS: Patients were treated with iGM-CSF 250 µg once a day given 4 days on and 4 days off for as long as necessary (the "as far as it takes" protocol). Upon remission, defined as absence of symptoms, oxygen desaturation <4 % at the walking test, and significant radiographic reduction of the infiltrates, or at least two of the above, the iGM-CSF dose was de-escalated. In the case of relapse, the patient was repositioned at the previous effective dose. Patients were investigated at 6-month intervals. To detect hematopoietic effects, blood cell counts, CD34+ cells, granulocyte macrophage progenitor colony-forming-units, and burst-forming-unit erythroid were measured. RESULTS: Six (five female) patients 43.8 ± 15.7 years of age were treated for 14-65 months and all responded to treatment. Remission was achieved after 25.6 ± 10 months. Three patients maintained remission at their lowest effective dose. Two patients relapsed at de-escalating doses. One patient remains on full-dose treatment. iGM-CSF had no impact on any of the hematological parameters tested. CONCLUSIONS: In aPAP, long-term adherence to the dose schedule permitted remission in all patients. Long-term treatment with iGM-CSF also permitted the definition of lower effective doses, minimizing disease burden and treatment costs safely, since no stimulating activity on hematopoiesis was observed, a fact that is of paramount importance for those aPAP patients needing lifelong treatment.

The Role of Cardiopulmonary Exercise Test in IPF Prognosis.

Background. In IPF, defects in lung mechanics and gas exchange manifest with exercise limitation due to dyspnea, the most prominent and disabling symptom. Aim. To evaluate the role of exercise testing through the 6MWT (6-minute walk test) and CPET (cardiopulmonary exercise testing) in the survival of patients with IPF. Methods. This is a prospective, observational study evaluating in 25 patients the relationship between exercise variables through both the 6MWT and CPET and survival. Results. By the end of the observational period 17 patients were alive (33% mortality). Observation ranged from 9 to 64 months. VE/VCO2 slope (slope of relation between minute ventilation and CO2 production), VO2 peak/kg (peak oxygen consumption/kg), VE/VCO2 ratio at anaerobic threshold, 6MWT distance, desaturation, and DLCO% were significant predictors of survival while VE/VCO2 slope and VO2 peak/kg had the strongest correlation with outcome. The optimal model for mortality risk estimation was VO2 peak/kg + DLCO% combined. Furthermore, VE/VCO2 slope and VO2 peak/kg were correlated with distance and desaturation during the 6MWT. Conclusion. The integration of oxygen consumption and diffusing capacity proved to be a reliable predictor of survival because both variables reflect major underlying physiologic determinants of exercise limitation.

Sleep oxygen desaturation predicts survival in idiopathic pulmonary fibrosis.

BACKGROUND: Recent studies suggest poor sleep quality in patients with idiopathic pulmonary fibrosis (IPF). However, so far, the impact of IPF-related sleep breathing disorders (SBDs) on survival has not been extensively studied. METHODS: In a cohort of 31 (24 males) treatment-naïve, newly diagnosed consecutive IPF patients, we prospectively investigated the relationship of SBD parameters such as apnea-hypopnea index (AHI), maximal difference in oxygen saturation between wakefulness and sleep (maxdiff SpO2), and lowest sleep oxygen saturation (lowest SpO2) with clinical (survival, dyspnea, daytime sleepiness), pulmonary function, submaximal (6-min walk test [6MWT]) and maximal exercise variables (cardiopulmonary exercise test [CPET]), and right ventricular systolic pressure (RVSP). RESULTS: Sleep oxygen desaturation exceeded significantly that of maximal exercise (p < 0.001). Maxdiff SpO2 was inversely related to survival, DLCO%, and SpO2 after 6MWT, and directly with dyspnea, AHI, and RVSP. The lowest SpO2 was directly related to survival and to functional (TLC%, DLCO%) as well as submaximal and maximal exercise variables (6MWT distance, SpO2 after 6MWT, peak oxygen consumption/kg, SpO2 at peak exercise), while an inverse association with dyspnea score, AHI, and RVSP was observed. CONCLUSIONS: Our findings provide evidence that intermittent sleep oxygen desaturation significantly exceeds that of maximal exercise and is associated with survival in IPF patients. Furthermore, they imply the existence of a link between lung damage and apnea events resulting to the induction and severity of intermittent sleep oxygen desaturation that aggravate pulmonary arterial hypertension and influence IPF survival.

Bronchiolitis: adopting a unifying definition and a comprehensive etiological classification.

Bronchiolitis is an inflammatory and potentially fibrosing condition affecting mainly the intralobular conducting and transitional small airways. Secondary bronchiolitis participates in disease process of the airways and/or the surrounding lobular structures in the setting of several already defined clinical entities, mostly of known etiology, and occurs commonly. Primary or idiopathic bronchiolitis dominates and characterizes distinct clinical entities, all of unknown etiology, and occurs rarely. Secondary bronchiolitis regards infections, hypersensitivity disorders, the whole spectrum of smoking-related disorders, toxic fumes and gas inhalation, chronic aspiration, particle inhalation, drug-induced bronchiolar toxicities, sarcoidosis and neoplasms. Idiopathic or primary bronchiolitis defines clinicopathologic entities sufficiently different to be designated as separate disease entities and include cryptogenic constrictive bronchiolitis, diffuse panbronchiolitis, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, neuroendocrine hyperplasia in infants, bronchiolitis obliterans syndrome in lung and allogeneic hematopoietic cell transplantation, connective tissue disorders, inflammatory bowel disease and bronchiolitis obliterans organizing pneumonia. Most of the above are pathological descriptions used as clinical diagnosis. Acute bronchiolitis, though potentially life threatening, usually regresses. Any etiology chronic bronchiolitis contributes to morbidity and/or mortality if it persists and/or progresses to diffuse airway narrowing and distortion or complete obliteration. Bronchiolitis in specific settings leads to bronchiolectasis, resulting in bronchiectasis.

Combined pulmonary fibrosis and emphysema.

The advent of computed tomography permitted recognition of the coexistence of pulmonary fibrosis and emphysema (CPFE). Emphysema is usually encountered in the upper lobes preceding fibrosis of the lower lobes, and patients are smokers, predominantly male, with distinct physiologic profile characterized by preserved lung volumes and markedly reduced diffusion capacity. Actually, the term CPFE is reserved for the coexistence of any type and grade of radiological pulmonary emphysema and the idiopathic usual interstitial pneumonia computed tomography pattern as well as any pathologically confirmed case. CPFE is complicated by pulmonary hypertension, lung cancer and acute lung injury and may present different outcome than that of its components.

Static and dynamic mechanics of the murine lung after intratracheal bleomycin.

BACKGROUND: Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure. METHODS: Single intratracheal injections of saline (50 µL) or bleomycin (2 mg/Kg in 50 µL saline) were administered to C57BL/6 (n=40) and Balb/c (n=32) mice. Injury/fibrosis score, tissue volume density (TVD), collagen content, airway resistance (RN), tissue damping (G) and elastance coefficient (H), hysteresivity (η), and area of pressure-volume curve (PV-A) were determined after 7 and 21 days (inflammation and fibrosis stage, respectively). Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests. RESULTS: Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls. CONCLUSIONS: Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.

Medical Research Council dyspnea scale does not relate to fibroblast foci profusion in IPF.

BACKGROUND: In Idiopathic pulmonary fibrosis (IPF) irreversibly progressive fibrosing parenchymal damage, leads to defects in mechanics and gas exchange, manifesting with disabling exertional dyspnea. Previous studies have shown a relationship between fibroblast foci (FF) profusion and severity and survival and a relationship between dyspnea grade and severity and outcome. We hypothesized a relationship between Medical Research Council (MRC) dyspnea scale with FF, and a relationship between FF and functional parameters and survival. METHODS: We retrospectively reviewed 24 histologically documented IPF patients. Profusion of FF was semiquantitatively evaluated by two scores, Brompton and Michigan. Survival analysis was performed by fitting Cox regression models to examine the relationship of the two scores with survival and the non-parametric Spearman correlation coefficient was calculated to describe the relationships of FF scores with dyspnea scores and functional parameters. RESULTS: No statistically significant correlation between FF scores and the MRC scores was observed (p = 0.96 and p = 0.508 respectively). No significant correlation between FF scores and survival (p = 0.438 and p = 0.861 respectively) or any functional parameter was observed. CONCLUSIONS: The lack of relationship between the MRC dyspnea scale and the FF might relate to the fact that dyspnea in IPF better reflects the overall of lung damage and its related consequences on mechanics and gas exchange whereas FF, one of its histological hallmarks, may not reflect its entire histology derangement also constrained by the geographically limited sampled tissue. This might be also valid for the observed lack of association between FF and survival or functional parameters.

MRC chronic Dyspnea Scale: Relationships with cardiopulmonary exercise testing and 6-minute walk test in idiopathic pulmonary fibrosis patients: a prospective study.

BACKGROUND: Exertional dyspnea is the most prominent and disabling feature in idiopathic pulmonary fibrosis (IPF). The Medical Research Chronic (MRC) chronic dyspnea score as well as physiological measurements obtained during cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) are shown to provide information on the severity and survival of disease. METHODS: We prospectively recruited IPF patients and examined the relationship between the MRC score and either CPET or 6MWT parameters known to reflect physiologic derangements limiting exercise capacity in IPF patients RESULTS: Twenty-five patients with IPF were included in the study. Significant correlations were found between the MRC score and the distance (r = -.781, p < 0.001), the SPO2 at the initiation and the end (r = -.542, p = 0.005 and r = -.713, p < 0.001 respectively) and the desaturation index (r = .634, p = 0.001) for the 6MWT; the MRC score and VO2 peak/kg (r = -.731, p < 0.001), SPO2 at peak exercise (r = -. 682, p < 0.001), VE/VCO2 slope (r = .731, p < 0.001), VE/VCO2 at AT (r = .630, p = 0.002) and the Borg scale at peak exercise (r = .50, p = 0.01) for the CPET. In multiple logistic regression analysis, the only variable independently related to the MRC is the distance walked at the 6MWT. CONCLUSION: In this population of IPF patients a good correlation was found between the MRC chronic dyspnoea score and physiological parameters obtained during maximal and submaximal exercise testing known to reflect ventilatory impairment and exercise limitation as well as disease severity and survival. This finding is described for the first time in the literature in this group of patients as far as we know and could explain why a simple chronic dyspnea score provides reliable prognostic information on IPF.

Amiodarone: review of pulmonary effects and toxicity.

Amiodarone, a bi-iodinated benzofuran derivative, is, because of its high effectiveness, one of the most widely used antiarrhythmic agents. However, adverse effects, especially potentially fatal and non-reversible acute and chronic pulmonary toxicity, continue to be observed. This review provides an update of the epidemiology, pathophysiology, clinical presentation, treatment and outcome of amiodarone pulmonary effects and toxicity. Lung adverse effects occur in approximately 5% of treated patients. The development of lung complications appears to be associated with older age, duration of treatment and cumulative dosage, high levels of its desethyl metabolite, history of cardiothoracic surgery and/or use of high oxygen mixtures, use of iodinated contrast media, and probably pre-existing lung disease as well as co-existing respiratory infections. Amiodarone-related adverse pulmonary effects may develop as early as from the first few days of treatment to several years later. The onset of pulmonary toxicity may be either insidious or rapidly progressive. Cough, new chest infiltrates in imaging studies and reduced lung diffusing capacity in the appropriate clinical setting of amiodarone use, after the meticulous exclusion of infection, malignancy and pulmonary oedema, are the cardinal clinical and laboratory elements for diagnosis. Pulmonary involvement falls into two categories of different grades of clinical significance: (i) the ubiquitous 'lipoid pneumonia', the so-called 'amiodarone effect', which is usually asymptomatic; and (ii) the more appropriately named 'amiodarone toxicity', which includes several distinct clinical entities related to the differing patterns of lung inflammatory reaction, such as eosinophilic pneumonia, chronic organizing pneumonia, acute fibrinous organizing pneumonia, nodules or mass-like lesions, nonspecific interstitial pneumonia-like and idiopathic pulmonary fibrosis-like interstitial pneumonia, desquamative interstitial pneumonia, acute lung injury/acute respiratory distress syndrome (ARDS) and diffuse alveolar haemorrhage. Pleural/pericardial involvement may be observed. Three different and intertwined mechanisms of lung toxicity have been suggested: (i) a direct toxic effect; (ii) an immune-mediated mechanism; and (iii) the angiotensin enzyme system activation. Mortality ranges from 9% for those who develop chronic pneumonia to 50% for those who develop ARDS. Discontinuation of the drug, control of risk factors and, in the more severe cases, corticosteroids may be of therapeutic value. Supportive measures for supervening ARDS in the intensive care setting may become necessary.

Clinical review: idiopathic pulmonary fibrosis acute exacerbations--unravelling Ariadne's thread.

Idiopathic pulmonary fibrosis (IPF) is a dreadful, chronic, and irreversibly progressive fibrosing disease leading to death in all patients affected, and IPF acute exacerbations constitute the most devastating complication during its clinical course. IPF exacerbations are subacute/acute, clinically significant deteriorations of unidentifiable cause that usually transform the slow and more or less steady disease decline to the unexpected appearance of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) ending in death. The histological picture is that of diffuse alveolar damage (DAD), which is the tissue counterpart of ARDS, upon usual interstitial pneumonia, which is the tissue equivalent of IPF. ALI/ARDS and acute interstitial pneumonia share with IPF exacerbations the tissue damage pattern of DAD. 'Treatment' with high-dose corticosteroids with or without an immunosuppressant proved ineffective and represents the coup de grace for these patients. Provision of excellent supportive care and the search for and treatment of the 'underlying cause' remain the only options. IPF exacerbations require rapid decisions about when and whether to initiate mechanical support. Admission to an intensive care unit (ICU) is a particular clinical and ethical challenge because of the extremely poor outcome. Transplantation in the ICU setting often presents insurmountable difficulties.

Acute severe asthma: new approaches to assessment and treatment.

The precise definition of a severe asthmatic exacerbation is an issue that presents difficulties. The term 'status asthmaticus' relates severity to outcome and has been used to define a severe asthmatic exacerbation that does not respond to and/or perilously delays the repetitive or continuous administration of short-acting inhaled beta(2)-adrenergic receptor agonists (SABA) in the emergency setting. However, a number of limitations exist concerning the quantification of unresponsiveness. Therefore, the term 'acute severe asthma' is widely used, relating severity mostly to a combination of the presenting signs and symptoms and the severity of the cardiorespiratory abnormalities observed, although it is well known that presentation does not foretell outcome. In an acute severe asthma episode, close observation plus aggressive administration of bronchodilators (SABAs plus ipratropium bromide via a nebulizer driven by oxygen) and oral or intravenous corticosteroids are necessary to arrest the progression to severe hypercapnic respiratory failure leading to a decrease in consciousness that requires intensive care unit (ICU) admission and, eventually, ventilatory support. Adjunctive therapies (intravenous magnesium sulfate and/or others) should be considered in order to avoid intubation. Management after admission to the hospital ward because of an incomplete response is similar. The decision to intubate is essentially based on clinical judgement. Although cardiac or respiratory arrest represents an absolute indication for intubation, the usual picture is that of a conscious patient struggling to breathe. Factors associated with the increased likelihood of intubation include exhaustion and fatigue despite maximal therapy, deteriorating mental status, refractory hypoxaemia, increasing hypercapnia, haemodynamic instability and impending coma or apnoea. To intubate, sedation is indicated in order to improve comfort, safety and patient-ventilator synchrony, while at the same time decrease oxygen consumption and carbon dioxide production. Benzodiazepines can be safely used for sedation of the asthmatic patient, but time to awakening after discontinuation is prolonged and difficult to predict. The most common alternative is propofol, which is attractive in patients with sudden-onset (near-fatal) asthma who may be eligible for extubation within a few hours, because it can be titrated rapidly to a deep sedation level and has rapid reversal after discontinuation; in addition, it possesses bronchodilatory properties. The addition of an opioid (fentanyl or remifentanil) administered by continuous infusion to benzodiazepines or propofol is often desirable in order to provide amnesia, sedation, analgesia and respiratory drive suppression. Acute severe asthma is characterized by severe pulmonary hyperinflation due to marked limitation of the expiratory flow. Therefore, the main objective of the initial ventilator management is 2-fold: to ensure adequate gas exchange and to prevent further hyperinflation and ventilator-associated lung injury. This may require hypoventilation of the patient and higher arterial carbon dioxide (PaCO(2)) levels and a more acidic pH. This does not apply to asthmatic patients intubated for cardiac or respiratory arrest. In this setting the post-anoxic brain oedema might demand more careful management of PaCO(2) levels to prevent further elevation of intracranial pressure and subsequent complications. Monitoring lung mechanics is of paramount importance for the safe ventilation of patients with status asthmaticus. The first line of specific pharmacological therapy in ventilated asthmatic patients remains bronchodilation with a SABA, typically salbutamol (albuterol). Administration techniques include nebulizers or metered-dose inhalers with spacers. Systemic corticosteroids are critical components of therapy and should be administered to all ventilated patients, although the dose of systemic corticosteroids in mechanically ventilated asthmatic patients remains controversial. Anticholinergics, inhaled corticosteroids, leukotriene receptor antagonists and methylxanthines offer little benefit, and clinical data favouring their use are lacking. In conclusion, expertise, perseverance, judicious decisions and practice of evidence-based medicine are of paramount importance for successful outcomes for patients with acute severe asthma.