Emergence of Aspergillus fumigatus azole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes.

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in patients with chronic obstructive pulmonary disease (COPD) but has not been specifically assessed so far. Here, we evaluated ARAF prevalence in azole-naïve COPD patients and their homes, and assessed whether CYP51A mutations were similar in clinical and environmental reservoirs. Sixty respiratory samples from 41 COPD patients with acute exacerbation and environmental samples from 36 of these patient's homes were prospectively collected. A. fumigatus was detected in respiratory samples from 11 of 41 patients (27%) and in 15 of 36 domiciles (42%). Cyp51A sequencing and selection on itraconazole medium of clinical (n = 68) and environmental (n = 48) isolates yielded ARAF detection in 1 of 11 A. fumigatus colonized patients with COPD (9%) and 2 of 15 A. fumigatus-positive patient's homes (13%). The clinical isolate had no CYP51A mutation. Two environmental isolates from two patients harbored TR34 /L98H mutation, and one had an H285Y mutation. Coexistence of different cyp51A genotypes and/or azole resistance profiles was detected in 3 of 8 respiratory and 2 of 10 environmental samples with more than one isolate, confirming the need for a systematic screening of all clinically relevant isolates. The high prevalence of ARAF in patients with COPD and their homes supports the need for further studies to assess the prevalence of azole resistance in patients with Aspergillus diseases in Northern France.

[Follow-up strategies for lung transplant recipients in France]. / Suivi partagé des patients transplantés pulmonaires.

BACKGROUND: Lung transplantation (LT) requires sustained care for a frequently polypathological condition. Follow-up is focused on three main issues: 1/stability of respiratory function; 2/comorbidity management; 3/preventive medicine. About 3000 LT patients in France are treated in 11 LT centers. Given the increased size of the LT recipient cohort, follow-up might be partially shared with peripheral centers. METHODS: This paper presents the suggestions of a working group of the SPLF (French-speaking respiratory medicine society) on possible modalities of shared follow-up. RESULTS: While the main LT center is tasked with centralizing follow-up, particularly the choice of optimal immunosuppression, an identified peripheral center (PC) may serve as an alternative to deal with acute events, comorbidities and routine assessment. Communication between the different centers should be free-flowing. Shared follow-up may be offered from the 3rd postoperative year to stable and consenting patients, whereas unstable and non-observant patients are poor candidates. CONCLUSION: These guidelines may serve as a reference for any pneumologist wishing to effectively contribute to follow-up, even and especially subsequent to lung transplant.

The Borg dyspnoea score: a relevant clinical marker of inspiratory muscle weakness in amyotrophic lateral sclerosis.

The aim of the study was to determine whether the Borg dyspnoea scale could be a useful and simple marker to predict respiratory muscle weakness in amyotrophic lateral sclerosis (ALS). From April 1997 to 2001, respiratory function was perfomed in 72 patients together with the Borg score in both the upright (uBorg) and supine (sBorg) positions. Mean upright vital capacity (VC) was 81+/-24% predicted, sniff nasal inspiratory pressure (SNIP) was 55+/-26% pred, maximal inspiratory pressure (P(I,max)) was 57+/-26% pred and arterial carbon dioxide tension (P(a,CO(2))) was 41+/-6 mmHg. The mean Borg scores in the upright and supine positions were 1.7+/-1.5 and 2.2+/-2, respectively. A significant relationship between SNIP and uBorg (r = 0.4; p = 0.0007) and SNIP and sBorg (r = 0.58; p<0.0001) was observed. Upright VC, DeltaVC (measured as the supine fall in VC as a percentage of seated VC), P(I,max) and P(a,CO(2)) were significantly correlated with SNIP. A cut-off value of 3 on the sBorg scale provided the best sensitivity (80%) and specificity (78%) (area under the curve 0.8) to predict a SNIP < or =40 cmH(2)O, indicating severe inspiratory muscle weakness. Patients with a sBorg score > or =3 also exhibited significantly lower VC, P(I,max) and twitch mouth pressure during cervical magnetic stimulation, and slightly higher P(a,CO(2)) (43.7+/-7 versus 39.2+/-5 mmHg; p = 0.05). The Borg dyspnoea scale is a valuable noninvasive test for the prediction of inspiratory muscle weakness in ALS patients.

[Idiopathic pulmonary fibrosis and right-to left shunt by patent foramen ovale]. / Fibrose pulmonaire idiopathique et shunt droit-gauche par foramen ovale perméable: amélioration clinique et gazométrique après fermeture percutanée.

INTRODUCTION: The association between idiopathic pulmonary fibrosis and patent foramen ovale has rarely been described. OBSERVATION: We report the cases of two patients, 72 and 59 years old, who presented with refractory hypoxemia in the context of pulmonary fibrosis. The hypoxemia was due to a right-to-left shunt through a patent foramen ovale (PFO), diagnosed by transoesophageal contrast echocardiography. The closure of the PFO allowed a decrease in the oxygen requirement in the first case: from 8 l/min to 3 l/min (PaO2 80 mmHg), and in the second case oxygen therapy could be stopped (PaO2 76 mmHg on room air). Right-to left shunts by PFO are usually associated with pulmonary arterial hypertension (systolic pulmonary arterial pressure at 70 mmHg for case 1), but in some cases the pulmonary artery pressure is normal (case 2), the shunt being due to an anatomical conformation. CONCLUSION: These two cases underline the importance of diagnosing right-to-left shunts in patients who have pulmonary fibrosis with severe hypoxemia, in order to reduce their oxygen needs.

[Rheumatoid arthritis and cystic fibrosis]. / Polyarthrite rhumatoïde et mucoviscidose.

INTRODUCTION: Inflammatory arthropathies are rare complications of cystic fibrosis (CF). We describe three cases of rheumatoid arthritis (RA) occurring in patients with this disease. OBSERVATIONS: Among the 100 patients under the care of the adult CF centre in Lille 3 presented with RA. This developed at the ages of 17, 44 and 19 years with a FEV1 of 53%, 42% and 94% respectively. They were 2 women and 1 man, with CFTR gene mutation delta F508 (1 homozygote and 2 heterozygotes) and positive sweat tests. They were colonised with Staphylococcus aureus, and rheumatoid factor and/or anti CCP antibodies were positive. The appearance and progression of RA were associated with exacerbations of bronchial infection and deterioration of respiratory function. In 2 patients the RA was continuously progressive despite intensive treatment involving high dose cortico-steroids, methotrexate (ineffective) followed by leflunomide (complicated by intractable respiratory infection). CONCLUSION: There is an increased incidence of RA in our patient population with CF. The new serum markers of RA including anti CCP are of diagnostic interest. The evolution of the two diseases is related and seems to be dependent on the level of infection leading to therapeutic problems.

[Exercise performance of patients with alveolar proteinosis]. / Comportement a l'exercice des patients atteints de protéinose alvéolaire.

INTRODUCTION: Cardiopulmonary exercise testing (CPET) is used to evaluate the severity of interstitial lung diseases, particularly when lung function is normal. The aim of this study was to analyse exercise capacity of patients with alveolar proteinosis. METHODS: We studied 7 patients undergoing alveolar proteinosis (aged 38 +/- 5 years), Three patients complained of exertional dyspnoea, 2 had a reduced vital capacity and 5 had a DLCO of less than 75% predicted. CPET was performed on a bicycle ergometer using a standard incremental protocol. RESULTS: CPET was symptom limited for all patients.. At peak exercise, VO2 was severely reduced (19.5 +/- 5.2 ml/kg/min, 58 +/- 9%). All patients developed hyperventilation. Ventilatory reserve was 42 +/- 11% of MMV, and dead space ratio (Vd/Vt) reached 0.29 +/- 0.05. Cardio-circulatory adaptation was normal (maximum heart rate 83 +/- 9%; VO2/heart rate 70 +/- 10%). Six patients exhibited gas exchange abnormalities at peak exercise (including 4 patients having a normal vital capacity): P(A-a)O2 56 +/- 18mm Hg; PaO2 65 +/- 18 mm Hg. CONCLUSION: Patients undergoing alveolar proteinosis have severe impairment of aerobic capacity and gas exchange on exercise. CPET appears to be useful for therapeutic management.

Physiologic correlates of dyspnea in patients with morbid obesity.

OBJECTIVE: Mechanisms of dyspnea in obesity remain unclear. This study was undertaken to determine the relationships between dyspnea and pulmonary function including inspiratory muscle endurance (IME) in morbidly obese patients before bariatric surgery. RESEARCH METHODS AND PROCEDURES: Fifty-five patients with a mean+/-s.d. body mass index (BMI) of 49.4+/-7.0 kg/m(2) were included. Dyspnea was evaluated by the Baseline Dyspnea Index (BDI; 0-12, 0=maximal dyspnea). Pulmonary function tests included a plethysmography, maximal inspiratory pressure (PImax) and IME was assessed by the incremental threshold loading test, determining the maximal pressure sustained for 2 min (Plim(2)) and Plim(2)/PImax ratio. Patients were classified according to their BMI in two groups: BMI < or =49 (n=27) and >49 kg/m(2) (n=28). RESULTS: Breathlessness was higher in the BMI >49 kg/m(2) group compared to the BMI < or =49 kg/m(2) group (BDI score at 6.9+/-2.2 in the BMI >49 kg/m(2) group vs 8.9+/-2.5 in the BMI < or =49 kg/m(2) group, P<0.01). Patients with BMI >49 kg/m(2) had significantly higher PaCO(2) level and significantly lower vital capacity, inspiratory capacity and PImax values compared with the BMI < or =49 kg/m(2) group. Correlations between BDI and lung function were moderate: forced expiratory volume in 1 s (FEV(1))% pred: Rho=0.27; P=0.05; vital capacity % pred: Rho=0.40; P=0.004; and Plim(2)/PImax: Rho=0.40; P=0.003. Higher correlations with dyspnea were found in the BMI < or =49 kg/m(2) group: FEV(1)% pred: Rho=0.38; P=0.05; and Plim(2)/PImax: Rho=0.49; P=0.01. DISCUSSION: Inspiratory muscle performance is moderately reduced in morbid obesity. Dyspnea in these patients remains moderately related to lung function and inspiratory muscle performance. However, inspiratory muscles performance correlates more significantly with dyspnea in patients with a BMI < or =49 kg/m(2).