[Graft-versus-host disease, a rare complication of lung transplantation]. / La maladie du greffon contre l'hôte, graft-versus-host disease, une complication exceptionnelle de la transplantation pulmonaire.

Graft-versus-host disease (GVHD) is a classic and frequent multisystemic complication of bone marrow allografts. It has also been reported after the transplantation of solid organs such as the liver or gut. Recent cases of GVHD have been reported after lung and heart-lung transplant. Skin, liver, gastrointestinal tract and bone marrow are the organ preferentially affected by GVHD. Corticosteroid is the first line treatment of GVHD. The prognosis reported in solid organ transplants is poor with infectious complications favoured by immunosuppressive therapy. In this article, we report a case of a patient with cystic fibrosis who presented a probable GVHD 18 months after a lung transplant and a literature review of similar cases.

[Indications of lung transplantation: Patients selection, timing of listing, and choice of procedure]. / Indications de la transplantation pulmonaire : sélection des candidats, critères d'inscription en liste d'attente, choix du type d'intervention.

Lung transplantation (LT) is now considered as an excellent treatment option for selected patients with end-stage pulmonary diseases, such as COPD, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension. The 2 goals of LT are to provide a survival benefit and to improve quality of life. The 3-step decision process leading to LT is discussed in this review. The first step is the selection of candidates, which requires a careful examination in order to check absolute and relative contraindications. The second step is the timing of listing for LT; it requires the knowledge of disease-specific prognostic factors available in international guidelines, and discussed in this paper. The third step is the choice of procedure: indications of heart-lung, single-lung, and bilateral-lung transplantation are described. In conclusion, this document provides guidelines to help pulmonologists in the referral and selection processes of candidates for transplantation in order to optimize the outcome of LT.

Tacrolimus-related cerebral microbleeds after lung transplantation.

Posterior reversible encephalopathy syndrome is a well-known complication of treatment by tacrolimus. We report 2 cases of lung transplant recipients treated with tacrolimus who developed cerebral microbleeds on T2∗-weighted sequences in the acute setting of posterior reversible encephalopathy syndrome. Cerebral microbleeds may be a marker of tacrolimus-induced vasculopathy that may be detected earlier by neuropsychological and magnetic resonance imaging monitoring in transplant recipients treated with tacrolimus.

Legionellosis and lung abscesses: contribution of legionella quantitative real-time PCR to an adapted followup.

We report a case of severe Legionnaires' disease (LD) complicated by a lung abscess in an immunocompetent patient who required ECMO therapy and thoracic surgery. The results of repeated Legionella quantitative real-time PCR performed on both sera and respiratory samples correlated with the LD severity and the poor clinical outcome. Moreover, the PCR allowed for the detection of Legionella DNA in the lung abscess specimen, which was negative when cultured for Legionella. This case report provides a logical basis for further investigations to examine whether the Legionella quantitative PCR could improve the assessment of LD severity and constitute a prognostic marker.

[Bronchiolo-alveolar carcinoma and lung transplantation]. / Carcinome bronchioloalvéolaire et transplantation pulmonaire.

INTRODUCTION: Bronchiolo-alveolar carcinoma is a controversial indication for lung transplantation because of the risk of recurrence. We report three cases and propose some risk factors for recurrence. CASE REPORTS: Our study concerns three patients transplanted at the Louis-Pradel Hospital between 1991 and 2010. The first patient relapsed 86 months after transplantation, benefited from surgical treatment, then died of renal failure. A second patient died of infection, without recurrence, 72 months after transplantation. The third had an early recurrence at 7 months and died 27 months after transplantation. The risk factors for recurrence appear to be: clinically "aggressive" presentation and histological stromal pulmonary invasion by the carcinoma. CONCLUSION: Diffuse bronchiolo-alveolar carcinoma is a possible indication of lung transplantation. The risk of recurrence imposes some requirements: a precise histological diagnosis and a slow clinical course.

Pulmonary zygomycosis in solid organ transplant recipients in the current era.

Fifty-eight solid organ transplant recipients with zygomycosis were studied to assess the presentation, radiographic characteristics, risks for extra-pulmonary dissemination and mortality of pulmonary zygomycosis. Pulmonary zygomycosis was documented in 31 patients (53%) and developed a median of 5.5 months (interquartile range, 2-11 months) posttransplantation. In all, 74.2% (23/31) of the patients had zygomycosis limited to the lungs and 25.8% (8/31) had lung disease as part of disseminated zygomycosis; cutaneous/soft tissue (50%, 4/8) was the most common site of dissemination. Pulmonary disease presented most frequently as consolidation/mass lesions (29.0%), nodules (25.8%) and cavities (22.6%). Patients with disseminated disease were more likely to have Mycocladus corymbifer as the causative pathogen. The mortality rate at 90 days after the treatment was 45.2%. In summary, pulmonary zygomycosis is the most common manifestation in solid organ transplant recipients with zygomycosis, and disseminated disease often involves the cutaneous/soft tissue sites but not the brain.

Factors predicting survival following noninvasive ventilation in amyotrophic lateral sclerosis.

BACKGROUND/AIMS: The involvement of respiratory muscles is a major predicting factor for survival in amyotrophic lateral sclerosis (ALS). Recent studies show that noninvasive ventilation (NIV) can relieve symptoms of alveolar hypoventilation. However, factors predicting survival in ALS patients when treated with NIV need to be clarified. METHODS: We conducted a retrospective study of 33 consecutive ALS patients receiving NIV. Ten patients had bulbar onset. We determined the median survivals from onset, diagnosis and initiation of NIV and factors predicting survival. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. RESULTS: The median initial and maximal total uses of NIV were 10 and 14 h/24h. The overall median survival from ALS onset was 34.2 months and worsened with increasing age and bulbar onset of the disease. The median survival from initiation of NIV was 8.4 months and was significantly poorer in patients with advanced age or with airway mucus accumulation. Survival from initiation of NIV was not influenced by respiratory parameters or bulbar symptoms. CONCLUSION: Advanced age at diagnosis and airway mucus accumulation represent poorer prognostic factors of ALS patients treated with NIV. NIV is a helpful treatment of sleep-disordered breathing, including patients with bulbar involvement.

[Outcome in COPD patients treated with at-home, long-term, non-invasive ventilation]. / Devenir des patients BPCO traités par ventilation non invasive prolongée à domicile.

BACKGROUND: The use of domiciliary non-invasive positive pressure ventilation (NIPPV) is still controversial in stable hypercapnic COPD. METHODS: Records of COPD patients who received home NIPPV from 1990 to 2002 either following an acute exacerbation or because of stable hypercapnia were retrospectively reviewed. RESULTS: Thirty-seven patients receiving long term oxygen therapy for 50 +/- 47 months were included. At inclusion, their mean +/- SD: FEV1 was 27 +/- 9% predicted, inspiratory capacity was 45 +/- 14% predicted, PaO2 breathing room air was 50 +/- 10 mm Hg, PaCO2 breathing room air = 53 +/- 8 mm Hg, PaCO2 with oxygen was 60 +/- 9 mm Hg. Median survival with NIPPV was 41 months. The 1-year, 3-year and 5-year survival rates with NIPPV were 92%, 62% and 24% respectively. Twelve months after onset of home NIPPV, PaCO2 breathing room air and with oxygen were significantly lower (47 +/- 8 mm Hg, p = 0.028 and 53 +/- 8 mm Hg, p = 0.005, respectively), inspiratory capacity was significantly improved (54 +/- 18% predicted, p = 0.033). CONCLUSION: This study suggests that home NIPPV allows a lasting physiological stabilization in selected COPD patients, particularly those with an advanced disease, by reducing hypercapnia and improving inspiratory capacity.

[Tracheotomy management in home mechanical ventilation]. / La gestion de la trachéotomie chez les patients adultes sous assistance ventilatoire à domicile.

INTRODUCTION: Despite a large increase in the use of long term non-invasive ventilation domiciliary ventilation via a tracheostomy remains necessary in certain cases of severe respiratory insufficiency. The object of this article is to describe the technical and human management required in domiciliary ventilation by tracheostomy. PERSPECTIVES: From the setting up of invasive ventilation in the home the choice of a tracheostomy tube to suit the patient and the management of the cuff by the patient or the family requires special attention by the prescribing physician. Currently humidification of the circuit is usually achieved by means of a hot water humidifier. Aspiration techniques, the changing and cleaning of the tracheostomy tube and the correct use of the speaking system need to be taught to the patient and the relatives. The main complications of domiciliary ventilation by tracheostomy are linked to the presence of the tube in the trachea and either mechanical (stenosis, granulomata, tracheal-oesophageal fistula) or infections. CONCLUSIONS: The prescribing physician should call on health care providers whose staff are trained in domiciliary ventilation by tracheostomy and include in his team nurses who can continue the education of the patient and relatives.

[Treatment of obstructive sleep apnea syndrome with mandibular advancement appliances]. / Traitement du syndrome d'apnées obstructives du sommeil par les orthèses d'avancement mandibulaire.

Mandibular advancement device provide a therapeutic option for obstructive sleep apnea syndrome (OSAS). Clinical improvement has been proven in the different available studies, mainly on nocturnal respiratory events and quality of sleep. Less snoring have been noted by bed partners and objective studies have demonstrated a decrease in snoring frequency and intensity. The effects of these appliances on upper airways resistance syndrome is not yet well documented. The significant clinical improvement is secondary to the decrease in the occurrence of apneas and hypopneas. Polysomnographic improvement criteria with an apnea hypopnea index less than 10 per hour has been noted in certain cases, although no improvement or even worsening was noted in other cases. Sleep architecture has also changed in these patients, with a decrease in the time spent in stages 1 and 2, and an increase in the time spent in stages 3, 4 and rapid eye movement sleep. Micro-arousals are also reduced in number. Somnolence and loss of attention are improved; these have been evaluated subjectively or by a well known and approved somnolence scale. In some cases a test for vigilance was done. Our results are identical to those published in the different studies concerning respiratory events and sleep architecture.

[Outcome of adult patients with cystic fibrosis admitted to intensive care with respiratory failure: the role of non-invasive ventilation]. / Devenir des adultes mucoviscidosiques admis en réanimation pour décompensation respiratoire.

Recourse to mechanical ventilation may prove necessary in adult patients with cystic fibrosis who have reached the stage of severe respiratory insufficiency. We report the experience of an intensive care service using non-invasive ventilation (NIV) as the first step in the management of acute respiratory failure in these patients. The records of 16 patients with cystic fibrosis presenting with acute respiratory failure and treated with NIV were analysed retrospectively. The characteristics of the group were: mean age 26.9 +/- 9.5 years; mean FEV1 21.5 +/- 10.4% predicted; mean body mass index 16.8 +/- 2.1; mean Pa CO(2) on admission 66 +/- 15 mm Hg. The mean duration of NIV in the ICU was 10 +/- 7 days. Eight patients (50%) died after having been intubated on account of failure of NIV. The eight survivors were discharged home with long-term NIV (mean duration 235 +/- 158 days). Six of them have received a lung transplant. The mode of onset of respiratory failure was an important prognostic factor: a rapid onset (<7 days) was invariably associated with death, on the other hand a gradual deterioration (> 7 days) was noted in the eight patients able to leave the ICU. In conclusion NIV may be regarded as the treatment of choice in patients with cystic fibrosis admitted to ICU with respiratory failure. In the case of persistent hypercapnia after the acute episode long-term NIV may keep them stable while awaiting lung transplantation.

Constrictive bronchiolitis obliterans. Characterisation of fibrogenesis and lysyl oxidase expression patterns.

The process leading to irreversible fibrotic constriction of the bronchioles was studied in two cases of bronchiolitis obliterans (BO) after bone marrow transplantation. Because lysyl oxidase (LOX) is the main collagen cross-linking enzyme that might account for irreversible fibrosis, its expression was studied together with expression of extracellular matrix (ECM) proteins. Characteristic types of lesions could be distinguished on the basis of histological and immunohistological criteria. An inflammatory stage was characterised by infiltration restricted to the bronchioles by lymphocytes and dendritic cells. A fibro-inflammatory stage was characterised by the coexistence of a persistent immune cellular lesion pattern with further focal modelling of a sub-epithelial neo-synthesised connective matrix. LOX expression was observed at the tips of intra-luminal fibrotic protrusions, together with tenascin and cellular fibronectin. A fibrotic stage was characterised by dense ECM deposits spreading throughout the peri-bronchiolar connective tissue, resulting in bronchiole obliteration and final disappearance. In contrast to reversible cases of fibrosis, persistence of long-term LOX expression reflecting continuing fibrosing activity might account for the irreversible status of BO. Our two cases illustrated that, at inflammatory and fibro-inflammatory stages, BO may be stabilised by immunosuppressive treatment, while the persistence of LOX expression in the fibrotic stage might correspond to a disease that becomes irreversible and fatal.

Outcome of patients with idiopathic pulmonary fibrosis admitted to the ICU for respiratory failure.

STUDY OBJECTIVES: To analyze the outcome of acute respiratory failure (ARF) in patients with idiopathic pulmonary fibrosis (IPF), and to evaluate the benefits of invasive and noninvasive mechanical ventilation (MV). DESIGN: Retrospective study. SETTING: University hospital. PATIENTS: Fifteen consecutive patients with IPF referred to the ICU for ARF between January 1989 and June 1998. MEASUREMENTS AND RESULTS: Fifteen patients (mean +/- SD age, 64 +/- 10 years) were included. Eight patients had clinical, functional, and radiologic features of IPF, and the remaining seven patients also had biopsy specimen-proven IPF. The mean duration between diagnosis of IPF and admission to the ICU was 26.5 +/- 28 months. At the time of ICU admission, mean arterial blood gas levels were as follows: PaO(2)/fraction of inspired oxygen, 113 +/- 95; pH, 7.32 +/- 0.10; and PaCO(2), 55 +/- 21 mm Hg. All patients received MV; 12 patients required tracheal intubation, either at the time of ICU admission (n = 10) or after failure of noninvasive ventilation (NIV; n = 2); and 3 patients only received NIV. Three of the five patients receiving NIV died of respiratory failure. Eleven patients died in the ICU, either from hypoxemia (n = 8) or from septic shock (n = 3). Four patients were discharged alive from the ICU, and two of them died shortly thereafter. CONCLUSION: The outcome of patients with IPF referred to the ICU for ARF was very poor and not improved by MV. Without a clearly identified reversible cause of ARF, these patients should not benefit from admission to the ICU.

[Mandibular advancement orthoses used in the treatment of obstructive sleep apnea syndrome]. / Orthèses d'avancement mandibulaire utilisées comme traitement du syndrome d'apnée obstructive du sommeil.

Mandibular advancement devices represent a therapeutic option for obstructive sleep apnea syndrome (OSAS). Clinical improvement has been proven in the different available studies, mainly on nocturnal respiratory events and quality of sleep. Less snoring have been noted by bed partners and objective studies have demonstrated decrease in snoring frequency and intensity. The effect of these ortheses on upper airways resistance syndrome is not yet well documented. The significant clinical improvement is secondary to the decrease in the occurrence of apneas and hypopneas. Polysomnographic improvement criteria with an apnea hypopnea index less than 10 per hour has been noted in certain cases. Although no improvement or even worsening was noted in other cases. Sleep architecture has also changed in these patients, with a decrease in the time spent in stages 1 and 2, and an increase in the time spent in stages 3 and 4 and rapid eye movement sleep. Micro-arousals are also decreased in number certainly with the decrease in the occurrence of respiratory events. Somnolence and loss of attention are improved; these have been evaluated subjectively or by a well known and approved somnolence scale. In some cases a test for vigilance was done.

Principles of mandibular advancement device applied to the therapeutic of snoring and sleep apnea syndrome.

Mandibular advancement device (MAD) represents a therapeutic option for simple snoring to obstructive sleep apnea syndrome (OSAS). The different available studies report an improvement either on nocturnal respiratory events or on the quality of sleep. The decrease in the intensity of snoring is confirmed by the patient's partner and by objective studies. For the time being the effects of these mandibular advancement devices on the upper airway resistance syndrome has not yet been well documented. The significant clinical improvement is secondary to the decrease in apnea hypopnea index (AHI). A polysomnographically proved cure has been reported with AHI < 10/h. Sleep architecture is also improved with wearing MAD demonstrating a decrease in the time passed in stage 1 sleep and an increase in slow wave sleep and rapid eye movement sleep (REM). A decrease in microarousals index has been shown. Daytime vigilance disorders are subjectively and objectively less remarkable. Then MAD can be beneficial for mild to moderate SAOS.

Nocturnal hypoventilation in chronic respiratory failure (CRF) due to neuromuscular disease.

Decrease of respiratory muscle capacities in neuromuscular disease can lead to chronic respiratory failure with permanent alveolar hypoventilation. Respiratory centers elaborate a strategy of breathing dedicated to prevent overt respiratory muscles fatigue. This strategy may worsen chronic hypercapnia. During sleep, ventilation decreases because a lessening in respiratory centers function. During NREM sleep hypoventilation is only an exacerbation of what is seen during wakefulness. During REM sleep, atonia worsens much more hypoventilation particularly when diaphragmatic function is impaired. The effects of atonia are amplified by a very low reactivity of respiratory centers. Nocturnal mechanical ventilation improves nocturnal hypoventilation and daytime arterial blood gases (ABG). Mechanism of improvement in ABG and how nocturnal hypoventilation and diurnal hypoventilation interact, are still a matter of debate.

[Mandibular advancement orthotic for treatment of obstructive sleep apnea]. / Orthèses d'avancement mandibulaire utilisées comme traitement du syndrome d'apnée obstructive du sommeil.

Mandibular advancement devices represent a therapeutic option for obstructive sleep apnea syndrome (OSAS). Clinical improvement has been proved in the different available studies, mainly on nocturnal respiratory events and quality of sleep. Less snoring have been noted by bed partners and objective studies have demonstrated decrease in snoring frequency and intensity. The effect of these ortheses on upper airways resistance syndrome is not yet well documented. The significant clinical improvement is secondary to the decrease in the occurrence of apneas and hypopneas. Polysomnographic improvement criteria with an apnea hypopnea index less than 10 per hour has been noted in certain cases. Although no improvement or even worsening was noted in other cases. Sleep architecture has also changed in these patients, with a decrease in the time spent in stages 1 and 2, and an increase in the time spent in stages 3 and 4 and rapid eye movement sleep. Microarousals are also decreased in number certainly with the decrease in the occurrence of respiratory events. Somnolence and loss of attention are improved; these have been evaluated subjectively or by a well known and approved somnolence scale. In some cases a test for vigilance was done.

Effects of prone position on alveolar recruitment and oxygenation in acute lung injury.

OBJECTIVE: To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure. DESIGN: Prospective physiologic study. SETTING: Medical ICU two in a university hospital. PATIENTS: Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury/adult respiratory distress syndrome (ALI/ARDS) in whom PP was indicated. MEASUREMENTS AND RESULTS: We constructed the static inflation volume-pressure curves (V-P) of the respiratory system in the 12 patients and differentiated between lung and chest wall in ten of them. We determined the difference between end-expiratory lung volume on positive end-expiratory pressure (PEEP) and relaxation volume of the respiratory system on zero PEEP (delta FRC). The recruited alveolar volume was computed as the delta FRC times the ratio of static elastance of the respiratory system to the lung. These measurements together with arterial blood gases determination were made in supine position (SP1), after 1 h of PP and after 1 h of supine repositioning (SP2) at the same level of PEEP. The PaO2/FIO2 ratio improved from SP1 to PP (136 +/- 17 vs 204 +/- 24 mm Hg; p < 0.01). An PP-induced alveolar recruitment was found in five patients. The change in oxygenation correlated to the recruited volume. The static elastance of the chest wall decreased from 4.62 +/- 0.99 cmH2O/l in SP1 to 6.26 +/- 0.54 cmH2O/l in PP (p < 0.05) without any correlation to the change in oxygenation. CONCLUSIONS: Alveolar recruitment may be a mechanism of oxygenation improvement in some patients with acute hypoxemic respiratory failure. No correlation was found between change in oxygenation and chest wall elastic properties.