Anxiety and depression in cystic fibrosis.

Cystic fibrosis (CF) is the most common genetic disorders in the Caucasian population, with estimated between 70,000 and 100,000 patients worldwide. Even if improved diagnostics and clinical management have led to an increased life expectancy, CF still remains a disease that significantly impacts patients' life in terms of symptoms, daily functioning, psychological morbidity and health related quality of life. Available data suggest that symptoms of anxiety and depression, such as in other chronic conditions, are common features in CF patients and in their caregivers, with a significant impact on disease outcomes. In this review we analyze and discuss the findings of The International Depression and Anxiety Epidemiological Study (TIDES), recently published on Thorax. This study was aimed to determine the prevalence of symptoms of depression and anxiety in a large population of adolescents and adults with CF and in parents of children with CF, across eight European countries and the USA. The TIDES provides useful insights about the psychological/psychiatric comorbidities in CF and its conclusions are absolutely shareable. Nevertheless some doubts remain on the methods and the tools. Further investigation and understanding of anxiety and depression in CF (in terms of prevalence, association with clinical, psychological and sociocultural factors) is necessary and evidence is crescent that a global and multidisciplinary approach is wanted.

Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis: Prevalence and Hemodynamic Differences in Lung Transplant Recipients at Transplant Center's Referral Time.

INTRODUCTION: Single or bilateral lung transplantation is a therapeutic procedure for end-stage lung diseases. In particular, in cases of chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, patients can be referred to the transplant center late and with important comorbilities. Pulmonary hypertension (PH) associated with lung diseases not only is an index of poor outcome but also is an indication for bilateral procedure. METHODS: We conducted a retrospective observational study. We analyzed right heart catheterization in a consecutive series of patients who underwent lung transplantation from 2006 to 2014 for end-stage COPD and pulmonary fibrosis. RESULTS: We included in the study 73 patients (35 with fibrosis and 38 with COPD); prevalence of PH was higher in the COPD group (84.3% vs 31.4%), and with worse hemodynamic parameters (mean pulmonary artery pressure [30.3 mm Hg vs 24.1 mm Hg]). The majority of COPD patients presented mild or moderate PH, and fibrosis patients showed normal pulmonary arterial pressures. CONCLUSIONS: COPD patients are referred to the Transplant Center with a higher prevalence of PH because of an echocardiographic screening or a late referral, but many patients survive on the waiting list and undergo the procedure. On the other hand, patients transplanted with interstitial diseases have a lower prevalence of PH; this can be explained by an earlier referral or a higher mortality on the waiting list and a more aggressive and rapidly progressing disease.

Emphysema: coiling up the lungs, trick or treat?

Lung volume reduction coil (LVRC) treatment is a minimally-invasive technique planned to achieve an improvement of exercise capacity and pulmonary function in subjects with advanced emphysema and hyperinflation. It has been proposed together with other bronchoscopic lung volume reduction approaches to reduce lung hyperinflation in emphysema as less invasive alternatives to LVRS and are currently under clinical investigation. Following the successful early experiences in previous pilot trials, recent studies allow further investigation into the feasibility, safety and efficacy of LVR coil treatment in a multi-center setting in a larger group of patients. According to this studies we can state that LVR coil treatment results in significant clinical improvements in patients with severe emphysema, in multicenter analysis, with a good safety profile and sustained results for up to 1 year. The literature on endobronchial coils continues to look promising with an acceptable safety profile, and positive long-term follow-up data are certainly more and more available. However, further well-designed, blinded, placebo (or sham) controlled trials, and even randomized trials against LVRS (lung volume reduction surgery), are needed before routine clinical use can be recommended. This is true not only for endobronchial coils, but also for the whole field of bronchoscopic lung volume reduction.

Novelties in COPD prognosis: evolution of survival indexes.

Despite several techniques, such as non-invasive ventilation (NIV), have improved the outcome of the acute exacerbation, COPD remains affected by poor prognosis in the medium and long term. Moreover, the task of predicting prognosis remains a major challenge for respiratory physicians. In order to overcome this limitation, several indexes have been proposed to assess the COPD patient in his/her complexity. The rationale is that, by using numerical indexes physicians may improve their clinical judgment to tailor and share therapeutical choices, i.e. referring the patient for surgery or lung transplantation. On this ground, Almagro et al. recently proposed the CODEX index, as the latest evolution of the BODE through the BODEx (which takes into account exacerbations), by adding the evaluation of comorbidity to the severity of dyspnoea, airway obstruction and history of exacerbations. As afore mentioned, treatment of COPD with respiratory acidosis has been revolutionized by the use of NIV, by reducing the need for intubation and in-hospital mortality of patients with severe COPD exacerbations. Nowadays, new promising techniques, such as minimally invasive extracorporeal devices, may hasten the clearance of carbon dioxide and reduce the work of breathing and the need for ventilation of COPD patients. These techniques still lack of randomized controlled studies; however, the approach of extracorporeal CO2 removal has the potential to further improve the prognosis of severe exacerbation of COPD patients. In this paper we discuss the prognostic evaluation of patients affected by COPD through the evolution of dedicated indexes, which mirror the focus of current research on the disease.

Emphysema: coiling up the lungs, trick or treat?

Lung volume reduction coil (LVRC) treatment is a minimally-invasive technique planned to achieve an improvement of exercise capacity and pulmonary function in subjects with advanced emphysema and hyperinflation. It has been proposed together with other bronchoscopic lung volume reduction approaches to reduce lung hyperinflation in emphysema as less invasive alternatives to LVRS and are currently under clinical investigation. Following the successful early experiences in previous pilot trials, recent studies allow further investigation into the feasibility, safety and efficacy of LVR coil treatment in a multi-center setting in a larger group of patients. According to this studies we can state that LVR coil treatment results in significant clinical improvements in patients with severe emphysema, in multicenter analysis, with a good safety profile and sustained results for up to 1 year. The literature on endobronchial coils continues to look promising with an acceptable safety profile, and positive long-term follow-up data are certainly more and more available. However, further well-designed, blinded, placebo (or sham) controlled trials, and even randomized trials against LVRS (lung volume reduction surgery), are needed before routine clinical use can be recommended. This is true not only for endobronchial coils, but also for the whole field of bronchoscopic lung volume reduction.

Anxiety and depression in cystic fibrosis.

Cystic fibrosis (CF) is the most common genetic disorders in the Caucasian population, with estimated between 70,000 and 100,000 patients worldwide. Even if improved diagnostics and clinical management have led to an increased life expectancy, CF still remains a disease that significantly impacts patients' life in terms of symptoms, daily functioning, psychological morbidity and health related quality of life. Available data suggest that symptoms of anxiety and depression, such as in other chronic conditions, are common features in CF patients and in their caregivers, with a significant impact on disease outcomes. In this review we analyze and discuss the findings of The International Depression and Anxiety Epidemiological Study (TIDES), recently published on Thorax. This study was aimed to determine the prevalence of symptoms of depression and anxiety in a large population of adolescents and adults with CF and in parents of children with CF, across eight European countries and the USA. The TIDES provides useful insights about the psychological/psychiatric comorbidities in CF and its conclusions are absolutely shareable. Nevertheless some doubts remain on the methods and the tools. Further investigation and understanding of anxiety and depression in CF (in terms of prevalence, association with clinical, psychological and socio-cultural factors) is necessary and evidence is crescent that a global and multidisciplinary approach is wanted.

Pulmonary endarterectomy: the lancet first, tears for pills.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease due to the incomplete resolution of pulmonary emboli, leading to right heart failure, with a poor survival. Pulmonary endarterectomy (PEA) is the operation of choice for CTEPH. As there are no well-defined criteria to discriminate surgically accessible from inaccessible obstructive lesions, the operability assessment relies on the surgeon's experience. The recommended algorithms to perform a correct diagnosis of CTEPH still suggest the lung ventilation/perfusion scan, despite advances in computed tomography with 3-D reconstruction and magnetic resonance imaging. Selective pulmonary angiography is the gold standard to assess operability in CTEPH. Medical therapy should not be considered an alternative to PEA, as it should be reserved to patients with either peripheral disease, deemed inoperable by an experienced PEA surgeon, or persistent/recurrent pulmonary hypertension after PEA. Lung transplantation, when indicated, still represents a viable option for patients with either inoperable CTEPH or CTEPH with concomitant severe parenchymal lung disease that contraindicates PEA. The outcome of operable CTEPH is still best predicted after surgery. Remarkably, the recovery of exercise capacity is not as immediate as hemodynamic improvement, underlining the importance of early identification of surgical candidates before physical deconditioning.

Bronchial thermoplasty in severe asthma: food for thoughts.

Asthma is a complex inflammatory disorder of the airways characterized by airway hyper-responsiveness and variable, reversible, airflow obstruction. Bronchial thermoplasty (BT) is a new modality for treating asthma. It targets airway smooth muscles (ASM) by delivering a controlled specific amount of thermal energy (radiofrequency ablation) to the airway wall through a dedicated catheter. The use of bronchial thermoplasty has been widely discussed for its potential in the treatment of asthma, since it seems to be able to reduce the symptoms of asthma. The definitive study for BT (AIR2 trial) employed a randomized, double-blind, sham-controlled design and enrolled 288 subjects with severe persistent asthma from 30 US and international centers. The results of the AIR2 trial demonstrated clinically significant benefits of BT compared with the sham group at one year post-treatment, including an improvement in asthma-related quality of life, 32% reduction in severe exacerbations, 84% reduction in emergency department visits for asthma symptoms, and a 66% reduction in time lost from work/school/other daily activities because of asthma symptoms. Preclinical work showed that ASM is reduced after BT by at least 3 years after treatment. The recent article from the ARI2 trial study group analyses the long-term safety and effectiveness of BT in patients with severe persistent asthma and demonstrates the 5-year durability of the benefits of BT in the control of symptoms and safety. It supports the evidence that reduction in asthma attacks, ER visits, and hospitalizations for respiratory symptoms are maintained for at least 5 years. There is a pressing need to understand the underlying mechanism(s) of BT and how the delivered heat is translated into clinical benefit. This necessitates additional investigation to identify disease and patient characteristics that would enable accurate phenotyping of positive responders to avoid unnecessary procedures and risks.

Viral Infections in lung transplant recipients: devils or trolls?

Lung transplantation is a therapeutic option for end stage lung diseases. One of the most important topics in transplant management is the role of viral infections in chronic lung allograft dysfunction (CLAD) and in particular in acute rejection (AR). This review arise from a recent study BY Brideaux et al. that offers the opportunity to investigate deeply the incidence, risk factors, symptomatology and clinical outcome of respiratory viral infections. Although most respiratory viral infections cause self-limited upper respiratory diseases, lung transplant recipients (LTRs) are particularly prone to develop complications. The absence of symptoms is a pivotal problem in managing these patients as it can depend on absence of active replication or on the effect of immunosuppressive regimen. In one word viruses can be just passengers or aggressive drivers in a facilitated environment, and the potential damage is completely different, as the management. PCR samplings give us an idea of the presence but not the certainty of the activity of viruses, and this is another common problem in reading data. In Herpes Virus infections this problem can be overtaken by studying biological samples and immune response, balancing the presence (PCR) and the activity (shell vial) of viruses with specific immune response (elispot). In fact viral presence doesn't mean activity and activity doesn't mean pathology in case of competent immune response. All these data can be matched in every single patient and managed by a tailored approach, either monitoring or treating.

Pulmonary hypertension in COPD and lung transplantation: timing and procedures.

The prevalence of pulmonary hypertension (PH) in the general chronic obstructive pulmonary disease (COPD) population is undefined because stable COPD patients do not routinely undergo screening echocardiogram and right heart catheterization. Most studies published on this topic are focused on a highly selected group of patients with moderate to severe disease awaiting lung transplantation, since hemodynamic data from cardiac catheterization are part of the standard transplant evaluation. In a very recent article, Hurdman et al. studied the characteristics and outcomes, with a particular focus on mortality, of extensively phenotyped, consecutive patients with PH-COPD over a 9-year period. This article offers the opportunity to update the role of PH in COPD as a timer to propose lung transplantation, based on solid literature data on survival, and to select the best procedure (single or double lung transplant), since the outcome indexes based on the old GOLD classification according to FEV1 (1-4) and the new GOLD classification (A-D) have failed in purpose to define the correct timing, due to the lack of functional (6 minutes walking test) and nutritional (Body Mass Index) data. After a revision of available literature including the recent paper of Hurdman et al. we conclude that the timing for lung transplantation is easy to manage in case of severe PH-COPD. On the other hand mild and moderate PH-COPD are still object of debate for therapy, procedure timing and choice and rehabilitation. In other words, we have some confirms for a little percentage of patients, whilst many doubts still exist for the rest.

Usable donor lungs: exploring the hidden part of the iceberg.

Lung transplantation (LTx) remains the only effective treatment of selected patients suffering from end-stage respiratory disease. However, its main limitation is represented by the shortage of suitable organs. In the last years, LTx is progressively changing in the clinical arena and different strategies aiming to increase the number of usable donor lungs have been reported. Many efforts have been employed to improve management of donor during donation and to treat marginal or even initially rejected grafts ex-vivo. The evolving scenario is showing excellent clinical results of the employment of those strategies. Castleberry et al. analyzed outcomes of LTx using grafts coming from brain-dead donors experiencing cardiac arrest. They examined data from the United Network for Organ Sharing database and they showed comparable results with the use of such grafts suggesting a potential way to increase the number of lung transplant procedures. The article gives a strong message to all clinicians involved in the hard field of transplantation. For those taking care of donors, they should always consider donors suffering from cardiac arrest suitable for lung donation despite pulmonary function because gas exchange can be eventually optimized with ex-vivo perfusion techniques. On the other side, surgeons should feel more comfortable using such grafts. If these lungs have a normal function while in the donor, their use for clinical transplantation provides good results and if they are dysfunctional EVLP could allow a restoration of optimal oxygenation after retrieval.

COPD classification methods and informativeness on mortality: contrasting evidences.

Understanding whether the ABCD GOLD classification method is informative with respect to the spirometric classification of severity in predicting mortality of patients with chronic obstructive pulmonary disease (COPD) is subject of debate. The results of a study performed on a sample of the Norwegian population (HUNT2) were recently published. Such data showed the inferiority of ABCD classification in predicting mortality compared to the spirometric classification, which was considered the gold standard up to the 2011 version of GOLD guidelines. This result is not in line with the results of other studies that have shown the equivalence of the two classifications. The new GOLD classification seemed to be a step forward for what concerns understanding patient's needs, but it seems clear that the insertion of a single clinical variable to the spirometric data may not be exhaustive in describing all the phenomena related to a heterogeneous disease such as COPD. The publication of the HUNT study provides an opportunity to analyze how the evidence has been produced, which scientific speculations it offers, what considerations could be drawn and what further research would be appropriate.

New life for macrolides.

This article is an attempt to analyze and discuss the role and the purported mechanisms of azithromycin (AZM) in non-eosinophilic severe asthma, including antineutrophil activity, an effect on gastroesophageal reflux or antibacterial activity against an underlying chronic infection, such as Chlamydia pneumoniae. Macrolides have an expanding role in the therapy of chronic inflammatory diseases based on their additional anti-inflammatory and immunosuppressive properties. Many studies have been performed in lung transplantation field and maintenance treatment has been proved to be effective in cystic fibrosis, bronchiectasis, diffuse panbronchiolitis, and in bronchiolitis obliterans syndrome and in the prevention of exacerbations in patients with chronic obstructive pulmonary disease. Pathobiological studies of people with severe, refractory asthma focused on its heterogeneity encouraging more targeted and personalized approaches to asthma therapy. In neutrophilic asthma corticosteroids are not very effective, while the immunomodulatory action of macrolides is particularly relevant on neutrophils. Recently, The AZIthromycin in Severe ASThma (AZISAST) study, published on the April number of Thorax, provided evidences on the efficacy and safety of long-term add-on treatment with AZM in severe non-eosinophilic asthma. Despite concerns about an increased proportion of macrolide-resistant organism and about the effects of macrolides on cardiovascular events, there was no evidence of an increased risk of pneumonia or other adverse events. Because the AZISAST study was not able to demonstrate significant improvement in lung function and use of rescue medication, there is still a need for new data confirming the efficacy of AZM in severe non-eosinophilic asthma.

Ex vivo lung perfusion increases the pool of lung grafts: analysis of its potential and real impact on a lung transplant program.

BACKGROUND: Among the strategies to increase the number of lung transplants, ex vivo lung perfusion (EVLP) represents a novel technique to expand the donor pool. METHODS: Data from donors referred to our center were retrospectively analyzed to identify grafts that could potentially be potentially reconditioned by EVLP and for comparison with those obtained by clinical application of EVLP program in our center. RESULTS: Among 75 rejected lungs, 23 organs have been identified as potentially treatable with EVLP with a hypothetic increase of lung transplant activity of 53%. After the introduction of the EVLP program in our center, lung transplantation with reconditioned grafts was performed in 7 (23%) patients with a 30% increase in transplant procedures. CONCLUSION: Although less than expected, EVLP increased the number of lungs suitable for transplantation.

Tailored cytomegalovirus management in lung transplant recipient: a single-center experience.

INTRODUCTION: Among solid organ recipients lung transplant recipients are at highest risk to be affected by cytomegalovirus infection (CMV) or to die from CMV disease. Two strategies are usually adopted in the clinical management of transplant recipients: antiviral prophylaxis and pre-emptive therapy. METHODS: In our center we adopted from 2007 a combined prophylaxis with anti-CMV immunoglobulins in the first post-transplant year and antiviral therapy (gancyclovir or valgancyclovir) from post-transplant day 15 for 3 weeks and in case of CMV bronchoalveolar lavage specimen positivity (polymerase chain reaction or shell vial). Moreover, we studied specific cellular immune response by an Elispot assay to define responder patients by the number of spot forming units (<5 nonresponders, 5-20 weeks, 20-100 good, >100 very good responders). RESULTS: We reduced acute rejections (from 17% to 6%, odds ratio 3.25), lymphocytic bronchitis bronchiolitis (from 11% to 2%), and first-year CMV pneumonia after the first post-transplant month (from 6.4% to 1%). We showed in nonresponders an earlier onset (68 vs 204 post-transplant days) and a longer duration (>14 days vs <14 days) of infection (P < .05 for all referred data). DISCUSSION: The morbility reduction has been obtained by antiviral therapy, increasing costs and risk of side effects. Our more recent studies show a population with a good immune response that probably doesn't need a pharmacological intervention but just a strict follow-up. CONCLUSION: Our proposed strategy is now tailoring the therapy on immune response clinical application, limiting to the specimen positivity in nonresponders.

Evaluation of Epstein-Barr virus-specific immunologic response in solid organ transplant recipients with an enzyme-linked ImmunoSpot assay.

Epstein-Barr virus (EBV) is a γ-herpes virus, responsible for infectious mononucleosis in immunocompetent hosts. Cellular immunity appears rapidly during EBV primary infection, keeping it silent despite long-life persistence in B lymphocytes. Defects of the EBV-specific cellular immunity are supposed to be the basis of post-transplantation lymphoproliferative disorders, promoted by high levels of immunosuppression. We retrospectively reviewed 197 solid organ transplant recipients to investigate EBV-specific lymphocyte responsiveness using Enzyme-linked ImmunoSpot assay (EliSpot), which assesses the EBV-specific interferon (IFN)-γ producing peripheral blood mononuclear cells, and kinetics of EBV infection/reactivation post-transplantation using quantitative real-time polymerase chain reaction (PCR) on whole blood. Overall, 102 of the 197 patients (51.8%) showed EBV responsiveness at the EBV-EliSpot assay: 68 (66.6%) showed a persistently positive EBV response in 3 or more determinations and 34 (33.3%) had transient episodes of nonresponsiveness. Ninety-five (48.2%) patients were persistently EBV nonresponders. EBV-DNAemia data were available for 58 patients: 27.6% presented at least one episode of EBV-DNA occurrence. No differences were found in EBV-EliSpot response stratification between the groups of patients who experienced episodes of EBV reactivation and those without EBV-DNAemia. However, EBV DNAemia peak values tended to be higher in the first year post-transplantation in the group of patients with a persistent positive EBV-specific immune response. EBV viral load quantitation in blood and EliSpot EBV-specific immune response determination may represent a powerful tool for monitoring solid organ transplant recipients, guiding immunosuppression modulation in patients with active EBV replication.

FEV6 assessment in spirometric abnormalities screening: the first population-based study in Italian pharmacies.

AIM: In recent years, the FEV1/FEV in six seconds ratio has been proposed and validated as a parameter for screening of airways obstruction and restriction. In this context an electronic spirometry screening of pharmacy customers could lead to significant benefits such as improving the appropriateness of diagnostic test prescription and facilitating the early diagnosis of asthma and chronic obstructive pulmonary disease (COPD). METHODS: Customers of 500 pharmacies in the italian Piemonte region were proposed to test their ventilatory function by an electronic spirometer, PiKo-6®, to find out probably obstruction (pO) and probably restriction (pR). All tests have been carried out by purposely trained pharmacists. Moreover, data regarding sampled subjects' gender, age, height, weight, smoke, pharmacology and therapies used were registered. A web application has been created to collect and analyze the data. RESULTS: Male smokers confirmed a percentage of pO similar to the one predicted in obstructive lung disease (OLD) in international literature (7%); higher percentages of pO (8%) and pR (35%) were instead found in underweight people. When the data are broken down into therapeutic categories, the highest number of pO (12%) and pR (38%) was found in patients in therapy with bronchodilators, in diabetic patients (pR 41%), and in people treated with diuretics (pO 7%, pR 46%) CONCLUSION: Data seem to suggest the six-second spirometry as a valid screening tool for the detection of possible airway obstruction and restriction in pharmacies setting. Results point out the possibility of rationalizing the access to medical visits and of optimizing prescriptive appropriateness. The above mentioned points will lead to save public money and will strengthen the role of the Community Pharmacy as health posts of Italian Health National System.

Lung volume reduction surgery 10 years later.

AIM: The purpose of this study was to evaluate whether favorable short-term results in term of functional outcome and survival following lung volume reduction surgery persist for longer periods. Composite preoperative and early postoperative variables were analysed. METHODS: This study was conducted on 52 emphysematous patients who underwent lung volume reduction surgery (LVRS) from 1993 to 2000, through a delayed retrospective analysis that has allowed us to evaluate a long-term follow-up (10 years or more); lung function and other variables were considered with respect to survival; 11 patients submitted to lung transplantation were also evaluated. RESULTS: Upper lobe distribution of emphysema (P=0.02, HR:2.43) and systolic PAP (P=0.04, HR=2.11) were significantly correlated to survival in a multivariate analysis; these variables seem to identify a small subgroup of 14 patients with longer survival (more than 10 years). Lung transplantation performed in some worsening patients (mean FEV1%:17±4) showed a trend of better survival when we compared the observed survival (55±47 months) with expected survival (39.5±15 months) (P=ns). CONCLUSION: We conclude that LVRS can lead to a very long survival (10 years or more) in a small subgroup of patients, with improvement of pulmonary functional data. Some preoperative data (upper lobe distribution of emphysema and pulmonary arterial pressure) appear to predict survival. Lung transplantation can be offered to these patients, showing a trend to improved life expectancy.

Lung volume reduction surgery 10 years later.

AIM:The purpose of this study was to evaluate whether favorable short-term results in term of functional outcome and survival following lung volume reduction surgery persist for longer periods. Composite preoperative and early postoperative variables were analysed. METHODS: This study was conducted on 52 emphysematous patients who underwent lung volume reduction surgery (LVRS) from 1993 to 2000, through a delayed retrospective analysis that has allowed us to evaluate a long-term follow-up (10 years or more); lung function and other variables were considered with respect to survival; 11 patients submitted to lung transplantation were also evaluated. RESULTS:Upper lobe distribution of emphysema (P=0.02, HR:2.43) and systolic PAP (P=0.04, HR=2.11) were significantly correlated to survival in a multivariate analysis; these variables seem to identify a small subgroup of 14 patients with longer survival (more than 10 years). Lung transplantation performed in some worsening patients (mean FEV1%:17±4) showed a trend of better survival when we compared the observed survival (55±47 months) with expected survival (39.5±15 months) (P=ns). CONCLUSION: We conclude that LVRS can lead to a very long survival (10 years or more) in a small subgroup of patients, with improvement of pulmonary functional data. Some preoperative data (upper lobe distribution of emphysema and pulmonary arterial pressure) appear to predict survival. Lung transplantation can be offered to these patients, showing a trend to improved life expectancy.

Clinical impact of HSV-1 detection in the lower respiratory tract from hospitalized adult patients.

The occurrence and clinical impact of herpes simplex virus (HSV) were evaluated in 342 bronchoalveolar lavage specimens from 237 patients. HSV-1 and HSV-2 were detected in 32.1% and <1% of patients, respectively. A significant difference of HSV-1 prevalence and load was found in relation to admission to intensive care unit, mechanical ventilation and mortality within 28 days; in particular, a viral load ≥10(5) copies/mL bronchoalveolar lavage fluid was significantly associated with critical features. No association was found with immune status or other characteristics. Nine of 21 (42.9%) cases of ventilator-associated pneumonia were positive for HSV-1, with poor outcome in six.