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.

[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.

[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.

In vitro HIV-1 entry and replication in Langerhans cells may clarify the HIV-1 genome detection by PCR in epidermis of seropositive patients.

Being dendritic antigen-presenting cells in skin and mucous membrane, Langerhans cells (LC) occur in areas at risk for inoculation by human immunodeficiency virus (HIV), and the question whether LC act as a target, reservoir, or vector for transmission of HIV has given rise to much controversy. To address this question, we first analyzed the epidermal compartment of skin from patients seropositive for HIV DNA. Second, we tested the susceptibility of each cell type normally found in this compartment to in vitro infection by HIV-1. A non-denatured DNA was obtained from epidermal sheets after a thermochemical treatment of biopsies (0.5 M ethylenediaminetetraacetic acid (EDTA), pH 7.5 at 60 degrees C for 90 seconds). Optimization of amplification of viral genome was performed with three primer pairs derived from gag, env, and pol sequences. Polymerase chain reaction (PCR) products were analyzed by Southern blot. Viral genome was found in five of 11 HIV-seropositive patients. To control the permissivity of epidermal cell population for HIV, cells isolated from the epidermal sheet of normal skin by trypsinization were co-cultured with HIV-1-carrying promonocytic cells (U937) and observed by electron microscopy. After 3-6 h of co-culture, numerous virions were either tightly bound or apparently engaged in the process of internalization through receptor-mediated endocytosis. At day 4 of co-culture, some infected LC appeared to release mature viral particles through bud formation. The in vitro HIV-1 entry and replication in LC may confirm the presence of the HIV-1 genome by PCR in epidermis of seropositive patients. The consequences of the permissivity of LC for HIV on the antigen-presenting function remain to be determined.

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.

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.

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.

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.

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.

[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.

[Pulmonary and musculo-cutaneous thigh actinomycosis]. / Actinomycose pulmonaire et musculo-cutanée de la cuisse.

We report a case of actinomycosis presenting with both a thigh abscess and a pulmonary lesion. Diagnosis was obtained by biopsy of this abscess, showing sulfur granules and further identification of Actinomyces israelii together with Actinobacillus actinomycetemcomitans in culture. Furthermore. Actinomyces israelii was isolated from bronchial secretions.

[Subpleural air cysts. A complication of barotrauma during mechanical ventilation]. / Les kystes aériens sous-pleuraux. Une complication barotraumatique de la ventilation mécanique.

The presence of air in the interstitial pulmonary tissues is shown as interstitial emphysema and is often the first sign of barotrauma. It results from hyper-pressure in the airways occurring for the greater part of the time on some underlying pulmonary pathology. This extra alveolar air may diffuse into the interstitium and collect under the visceral pleura, appearing on radiographs as air cysts from 3 to 10 centimeters in diameter. We described 7 cases of air cysts occurring in adults on mechanical ventilation. The lesions seem to us to represent a radiological entity and evidence of barotrauma due to mechanical ventilation and possessing its own potential outcome, namely rupture leading to pneumothorax, infection, persistence, or disappearance. The early occurrence in its history of a particular disease should be noted, enabling one to minimise the factors contributing to the barotrauma.

[Lung complications of hematopoietic stem cell transplantation]. / Complications pulmonaires des greffes de cellules souches hématopoïétiques.

Bone marrow transplantation (BMT) is a potentially curative therapy in selected patients with hematologic disorders (acute leukemia, chronic myelogenous leukemia, lymphoma) or solid tumors (testicular or breast cancer). Pulmonary complications occur in 40 to 60% of patients receiving BMT, and are related to various mechanisms: chemotherapy-induced neutropenia, pulmonary toxicity of radiotherapy or chemotherapy, graft-versus-host disease. Bacterial or fungal pneumonia occurring during the initial period of neutropenia, and interstitial pneumonia (related to cytomegalovirus or of unknown origin) are the major respiratory complications of the first 100 days. Bacterial sinusitis and pulmonary infections, and obstructive airways disease related to bronchiolitis are the main late-onset respiratory disorders. No single risk factor can predict the development of these complications, which result from a sequence of events including infections, pulmonary injuries related to chemotherapy or radiotherapy, and inappropriate immunological reaction after transplantation. Antimicrobial prevention has been shown to reduce the mortality of these complications, but they still result in both important morbidity and mortality. They are the most frequent non relapse cause of death among long term surviving patients. Better understanding of their pathogenesis, and early recognition and treatment of respiratory complications of BMT should improve the efficacy of this therapy.

[Cutaneous Kaposi's sarcoma with pulmonary carcinomatous lymphangitis in patient with heart transplantation]. / Sarcome de Kaposi cutané avec lymphangite carcinomateuse pulmonaire chez un transplanté cardiaque.

The great strides in organ transplantation have been accompanied by some specific pathologies, notably, neoplasia, including Kaposi's sarcoma which occupies the third place in frequency after cutaneous tumours and malignant lymphomas. We report a case of cutaneous Kaposi's sarcoma developing some six months after a cardiac transplant. The modulation of immuno-suppression and treatment with Alpha interferon allowed an initial stabilisation of the cutaneous lesions. However, there were secondary developments of the lesions and, 21 months after the initial presentation, the patient developed a diffuse infiltrating pneumonia leading to death. The autopsy revealed lymphangitis carcinomatosis of Kaposi's sarcoma type. This observation underlines the therapeutic difficulties seen in Kaposi's sarcoma after organ transplantation when there is no alternative to allow a significant reduction or cessation of immuno-suppression.

[Bronchiolitis obliterans with severe obstructive ventilation disorder after a bone marrow transplant. Study of 7 cases]. / Bronchiolite oblitérante avec trouble ventilatoire obstructif sévère après allogreffe de moelle osseuse. Etude de 7 cas.

In 40 to 60% of bone marrow grafts there are pulmonary complications of which the most frequent is the occurrence of an interstitial pneumonia. We report 7 cases here of a more rare complication, that of bronchiolitis obliterans (BO). Between December 1979 and November 1989, 7 patients (3.4% of our cases of GMO) have developed over several months a chronic obstructive respiratory failure (a mean VEMS of 43% of the theoretical value) in the year following the transplantation (mean delay 190 days). 6 patients presented with cutaneous, digestive or hepatic signs of chronic graft v host illness (GVH) whereas the prevalence of this complication in the population studied was 17%. Treatment combining bronchodilators and immunosuppressants was only successful in 2 cases and the outcome was fatal in the 5 other cases as a result of respiratory failure (mean delay 208 days between the appearance of respiratory symptoms and death). The pathogenesis of BO after GMO remains poorly understood. It may rest on an immune process during the course of which the BO would be the result of a chronic pulmonary GVH. Another hypothesis is that the state of the immunosuppression in these patients would favour the appearance of a bronchiolitis of an infectious origin, particularly viral. The prognosis of BO after GMO is very poor and in the absence of specific effective treatment the therapeutic strategy remains essentially that of prevention by the early detection of respiratory anomalies.

[Bilateral diaphragmatic paralysis, the cause of acute insufficiency in chronic obstructive bronchopathy. The value of nasal mechanical ventilation]. / Paralysie diaphragmatique bilatérale, cause de décompensation aiguë d'une bronchopathie chronique obstructive. Intérêt de la ventilation mécanique par voie nasale.

A 57 year old man with chronic bronchitis sought a consultation for dyspnoea at rest associated with an absolute inability to lie flat. Examination revealed paradoxical respiration and respiratory function testing revealed a mixed ventilation disturbance, which was predominantly obstructive and was aggravated in the dorsal decubitus position. Radiology revealed bilateral diaphragmatic paralysis, which was confirmed on measurement of transdiaphragmatic pressure. The patient benefited from assisted ventilation by the nasal route with an excellent result in both the short and the medium term. Investigation into the cause was negative, in particular there was no evidence of any neuromuscular abnormality. This case recalls the role of the diaphragm in acute respiratory failure and shows the value of mechanical ventilation by the nasal route in the treatment of certain types of diaphragmatic paralysis.

[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.

[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.