Outcomes in progressive systemic sclerosis treated with autologous hematopoietic stem cell transplantation compared with combination therapy.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive systemic sclerosis (SSc) compared with cyclophosphamide. Cyclophosphamide, however, does not provide a long-term benefit in SSc. The combination of mycophenolate mofetil (MMF) and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab. METHODS: Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease > 25% or an FVC increase > 10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death. RESULTS: Twenty-one SSc patients in the combination therapy group were compared with sixteen in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (p= 0.7). The hazard ratio for EFS at 24 months favored the combination group (HR = 0.09, P= 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months. CONCLUSION: MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months.

Invasive Pulmonary Aspergillosis in Multiple Myeloma patients: A sizeable diagnosis in the era of novel anti-myeloma therapies.

BACKGROUND: Advances in treatment for multiple myeloma (MM) patients entail a high risk for opportunistic infections such as invasive pulmonary aspergillosis (IPA). OBJECTIVES: This study was conducted to describe the patient's profile, clinical manifestations, diagnosis and outcome of MM patients with IPA, in our large haemato-oncology centre. PATIENTS/METHODS: We retrospectively analysed patients with MM who underwent Broncho alveolar lavage for pneumonia at Rambam Hospital during a 13-year period from July 2005 to February 2018. We focused on those with Aspergillus pneumonia. RESULTS: Of the 669 patients with multiple myeloma, mean age 62.6 (±7.6) years, forty-two patients (6.2%) were diagnosed with IPA. Among them, 60% had a probable diagnosis and 40% possible. Clinical presentation was similar for IPA and other pulmonary infections. Compared to those with other pulmonary infections, IPA was more commonly diagnosed in patients with long-standing disease (p = .00012) and among patients receiving 3 or more lines of myeloma therapies (p = .04). Thirty-day mortality rates following diagnostic bronchoscopy did not differ between IPA and non-IPA patients. (p = .85). CONCLUSIONS: Multiple myeloma patients had an increased risk for IPA, most notably in patients with 3 or more lines of anti-myeloma treatment and more advanced disease. This clearly emphasises the vigilance needed for IPA in these patients.

Heparan sulfate chains contribute to the anticoagulant milieu in malignant pleural effusion.

BACKGROUND: While malignant pleural effusion (MPE) is a common and significant cause of morbidity in patients with cancer, current treatment options are limited. Human heparanase, involved in angiogenesis and metastasis, cleaves heparan sulfate (HS) side chains on the cell surface. AIMS: To explore the coagulation milieu in MPE and infectious pleural effusion (IPE) focusing on the involvement of heparanase. METHODS: Samples of 30 patients with MPE and 44 patients with IPE were evaluated in comparison to those of 33 patients with transudate pleural effusions, using heparanase ELISA, heparanase procoagulant activity assay, thrombin and factor Xa chromogenic assays and thromboelastography. A cell proliferation assay was performed. EMT-6 breast cancer cells were injected to the pleural cavity of mice. A peptide inhibiting heparanase activity was administered subcutaneously. RESULTS: Levels of heparanase, factor Xa and thrombin were significantly higher in exudate than transudate. Thromboelastography detected almost no thrombus formation in the whole blood, mainly on MPE addition. This effect was completely reversed by bacterial heparinase. Direct measurement revealed high levels of HS chains in pleural effusions. Higher proliferation was observed in tumour cell lines incubated with exudate than with transudate and it was reduced when bacterial heparinase was added. The tumour size in the pleural cavity of mice treated with the heparanase inhibitor were significantly smaller compared with control (p=0.005). CONCLUSIONS: HS chains released by heparanase form an anticoagulant milieu in MPE, preventing local thrombosis and enabling tumour cell proliferation. Inhibition of heparanase might provide a therapeutic option for patients with recurrent MPE.

Clinical Spectrum, Diagnosis and Outcome of Rare Fungal Infections in Patients with Hematological Malignancies: Experience of 15-Year Period from a Single Tertiary Medical Center.

BACKGROUND: Patients with hematological malignancies and allogeneic hematopoietic stem-cell transplant recipients carry a high risk of rare (non-Aspergillus molds and non-Candida yeasts) invasive fungal infections (IFI). METHODS: We retrospectively evaluated and described the patient profile, clinical manifestations, isolated species, treatment and outcome of patients with hematological malignancies diagnosed with these rare IFIs during 15 years in a large single hemato-oncology center. RESULTS: Eighty-seven patients with hematological malignancies treated in our center had at least one positive culture or molecular identification of a rare fungus. Ninety-three isolates were considered the etiological agents of the infection. The most common underlying hematological malignancy was acute myeloid leukemia, 36 patients (41.4%). Eighty patients (91%) received chemotherapy less than 30 days prior to IFI diagnosis. The most frequent site of infection was the respiratory tract: 34 patients (39%) had pulmonary and 19 patients (22%) had a sinusal or nasopharyngeal infections. Disseminated infection, defined as positive blood cultures or parallel infection in multiple organ systems, was documented in 20 patients (23%). The most common fungal species were Fusarium (35%) and Zygomycetes (25%). Coinfection with more than one fungus was noted in 20 patients (23%). Forty-seven of 87 patients (54%) in this study died within 90 days of IFI diagnosis. CONCLUSIONS: Rare IFIs in patients with hematological malignancy become increasingly frequent. Early identification with traditional and molecular methods is important in management of these patients.

Baseline Chest Computed Tomography for Early Diagnosis of Invasive Pulmonary Aspergillosis in Hemato-oncological Patients: A Prospective Cohort Study.

Invasive pulmonary aspergillosis (IPA) has dire consequences in hemato-oncological patients. We report our experience with performing routine baseline chest computed tomography for early diagnosis of IPA. We found high rates of proven or probable IPA diagnosed on admission among patients with newly diagnosed acute myeloid leukemia.

Community-acquired respiratory infections are common in patients with non-Hodgkin lymphoma and multiple myeloma.

PURPOSE: Available data suggest that respiratory infections are associated with increased morbidity and mortality in patients hospitalized due to acute leukemia and allogeneic stem cell transplantation (allo-SCT). However, the precise incidence, risk factors, and severity of respiratory infection, mainly community-acquired, in patients with lymphoma and multiple myeloma (MM) are not fully determined. The current study aimed to investigate risk factors for respiratory infections and their clinical significance in patients with B cell non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) in the first year of diagnosis. METHODS: Data of consecutive patients diagnosed with NHL or MM and treated at the Rambam Hematology Inpatient and Outpatient Units between 01/2011 and 03/2012 were evaluated. Information regarding anticancer treatment, incidence and course of respiratory infections, and infection-related outcomes was analyzed. RESULTS: One hundred and sixty episodes of respiratory infections were recorded in 103 (49%) of 211 (73-MM, 138-NHL) patients; 126 (79%) episodes were community-acquired, 47 (29%) of them required hospitalization. In univariate analysis, age < 60 years, MM diagnosis, and autologous SCT increased the respiratory infection risk (P = 0.058, 0.038, and 0.001, respectively). Ninety episodes (56% of all respiratory episodes) were examined for viral pathogens. Viral infections were documented in 25/90 (28%) episodes, 21 (84%) of them were community-acquired, requiring hospitalization in 5 (24%) cases. Anti-flu vaccination was performed in 119 (56%) patients. Two of the six patients diagnosed with influenza were vaccinated. CONCLUSIONS: Respiratory infections, including viral ones, are common in NHL and MM. Most infections are community-acquired and have a favorable outcome. Rapid identification of viral pathogens allows avoiding antibiotic overuse in this patient population.

[DIAGNOSIS AND TREATMENT OF BRONCHIECTASIS: POSITION PAPER OF THE ISRAELI PULMONOLOGY SOCIETY AND THE ISRAELI PEDIATRIC PULMONOLOGY SOCIETY].

INTRODUCTION: Bronchiectasis is anatomically defined by irreversible distortion of the bronchi. Clinically, its manifestations are cough with sputum production and a predisposition to pulmonary infections. Unlike asthma and COPD, where ample clinical data are present regarding the course and effective treatment, knowledge of bronchiectasis has yet to evolve. Lately, bronchiectasis is gaining renewed attention among the medical community, with growing basic and clinical research-based data. In Israel, no registered treatments exist for bronchiectasis, which makes it difficult to treat these patients. This paper is a summary of the position of the Israeli Pulmonology Association and the Israeli Pediatric Pulmonology Association for diagnosis and treatment of bronchiectasis.

Polymicrobial pulmonary infection in patients with hematological malignancies: prevalence, co-pathogens, course and outcome.

PURPOSE: The frequency and clinical significance of polymicrobial pneumonia in patients with hematological malignancies (HM) are poorly understood. The aim of the present study is to describe the prevalence, risk factors, clinical characteristics, and outcome of patients with HM and polymicrobial pneumonia. METHODS: Over a 5 year period, 436 consecutive adult patients with HM and pulmonary infiltrates underwent diagnostic fiberoptic bronchoscopy with bronchoalveolar lavage. For 219 patients an infectious etiology was diagnosed, of them 45 (20.5 %) had polymicrobial etiology. Risk factors, clinical course and outcome of polymicrobial pulmonary infection in patients with HM were established. RESULTS: 45 patients with HM were identified with polymicrobial pulmonary infection, 39 of them with two pathogens, and 6 with three. The most common co-pathogen identified was Aspergillus sp. (87 %). Allogeneic hematopoietic stem cell transplantation (HSCT) and graft versus host disease (GVHD) were predictors of polymicrobial infection. Compared to patients with monomicrobial pneumonia, patients with polymicrobialpulmonary infection had a more severe clinical course with more dyspnea (69 vs. 49 %, P = 0.016), hemoptysis (16 vs. 7 %, P = 0.065) and more required respiratory support (27 vs. 17 %, P = 0.125). In-hospital mortality was significantly higher in patients with polymicrobial pulmonary infection than in patients with monomicrobial pulmonary infection (49 vs. 19 %, P < 0.001). CONCLUSIONS: Polymicrobial pulmonary infection occurs quite frequently in patients with HM, especially in allogeneic HSCT recipients and in patients with GVHD. The clinical course of polymicrobial pulmonary infection is severe and mortality approaches 50 %. The clinician taking care of these patients should always look for additional copathogens in profoundly immunosuppressed patients with pneumonia.

Do Wound Cultures Give Information About the Microbiology of Blood Cultures in Severe Burn Patients?

BACKGROUND: Blood stream infection (BSI) and the subsequent development of sepsis are among the most common infection complications occurring in severe burn patients. This study was designed to evaluate the relationship between the burn wound flora and BSI pathogens. METHODS: Documentation of all bacterial and fungal wound and blood isolates from severe burn patients hospitalized in the burn unit and intensive care unit was obtained from medical records retrieved retrospectively from a computerized, hospital-wide database over a 13-year period. All data were recorded in relation to the Ryan score. RESULTS: Of 195 severe burn patients, 88 had at least 1 BSI episode. Transmission of the same pathogen from wound to blood was documented in 30% of the patients, with a rising BSI frequency as the Ryan score increased. There were a total of 263 bacteremic episodes in 88 study patients, 44% of blood isolates were documented previously in wound cultures, and transmission of the same pathogen from wound to blood was noted in 65% of bacteremic patients. CONCLUSIONS: When there is clinical suspicion of sepsis, appropriate empirical systemic antibiotic therapy should be broad spectrum and should rely on the susceptibility of the organisms from recent cultures of the burn wound surface, until the blood cultures results are completed.

Long-term follow-up of patients with scleroderma interstitial lung disease treated with intravenous cyclophosphamide pulse therapy: a single-center experience.

BACKGROUND: Scleroderma lung disease (ILD-SSc) is treated mainly with cyclophosphamide (CYC). The effectiveness of CYC was judged after 12-24 months in most reports. OBJECTIVES: To analyze the effect of monthly intravenous CYC on pulmonary function tests including forced vital capacity (FVC) and diffusing lung capacity (DLCO), as well as Rodnan skin score (mRSS), during long-term follow-up. METHODS: We retrospectively collected the data on 26 ILD-SSc patients who began CYC treatments before 2007. Changes in FVC, DLCO and mRSS before treatment, and at 1,4 and 7 years after completion of at least six monthly intravenous CYC treatments for ILD-SSc were analyzed. RESULTS: Mean cumulative CYC dose was 8.91 ± 3.25 G. More than 30% reduction in FVC (0%, 8%, and 31% of patients), DLCO (15%, 23%, 31%), and mRSS (31%, 54%, 62%) at years 1, 4 and 7 was registered. During the years 0-4 and 4-7, annual changes in FVC, DLCO and mRSS were 3.2 vs. 0.42% (P < 0.040), 4.6 vs. 0.89% (P < 0.001), and 1.8 vs. 0.2 (P = 0.002). The greatest annual FVC and DLCO reduction over the first 4 years correlated with mortality (P = 0.022). There were no differences in the main variables regarding doses of CYC (< 6 G and > 6 G). CONCLUSIONS: In patients with ILD-SSc, CYC stabilized the reduction of FVC during treatment, but this effect was not persistent. The vascular characteristic of ILD-SSc (DLCO) was not affected by CYC treatment. CYC rapidly improved the mRSS. This effect could be achieved with at least 6 G of CYC. Higher rates of annual reduction in FVC and DLCO in the first 4 years indicate the narrow window of opportunity and raise the question regarding ongoing immunosuppression following CYC infusions.

Low incidence of long-term respiratory impairment in Hodgkin lymphoma survivors.

Introduction of new chemotherapy regimens over the last decade resulted in 90% survival in patients with Hodgkin lymphoma (HL), which enhances significance of abrogating chemotherapy-related long-term toxicities in young subjects. The present trial evaluated incidence of long-term respiratory complications associated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin sulfate, etoposide phosphate, doxorubicin hydrochloride (Adriamycin), cyclophosphamide, vincristine sulfate (Oncovin), procarbazine hydrochloride, and prednisone (BEACOPP). Sixty-seven HL patients, 21 treated with ABVD and 46 with BEACOPP, underwent prospective respiratory evaluation. Median follow-up from chemotherapy completion to respiratory assessment was 61 months. Abnormal lung function tests (LFT) were found in nine patients (13.6%)-three with functional dyspnea and six asymptomatic-with reduced DLCO (≤70%), VC, and TLC. Previous history of bleomycin pulmonary toxicity was found to be the only statistically significant factor for chronic respiratory impairment (75% vs. 10%, p = 0.007, relative risk (RR) = 28; 95% CI, 2.5-313). However, abnormal LFT tended to occur more frequently in patients receiving mantle field irradiation (18% vs. 9%, RR = 2.2), those who experienced respiratory infection (25% vs. 13%, RR = 2.25), and patients treated with ABVD compared to BEACOPP (19% vs. 11%, RR = 1.9). Long-term respiratory impairment in HL survivors is unusual and rarely results in functional discomfort. BEACOPP is "respiratory safe," being associated with a nonsignificant risk for long-term respiratory dysfunction.

The increased risk for pneumocystis pneumonia in patients receiving rituximab-CHOP-14 can be prevented by the administration of trimethoprim/sulfamethoxazole: a single-center experience.

Recent studies suggest an increased risk for Pneumocystis jirovecii pneumonia (PJP) in adults receiving short-interval rituximab-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) therapy for diffuse large cell B cell lymphoma (DLBCL). This retrospective study evaluates precise PJP incidence and the efficacy of anti-PJP prophylaxis in DLBCL. Patients with DLBCL, aged ≥18 years and treated between December 2004 and December 2010, were included. Details of treatment-related respiratory infections, focusing on PJP incidence, risk factors and prophylaxis, were assessed. A total of 132 patients were analyzed; 47 were treated with rituximab-CHOP therapy every 21 days (R-CHOP-21) and 85 were treated every 14 days (R-CHOP-14). The incidence of treatment-related respiratory infections was higher in patients receiving R-CHOP-14. PJP was diagnosed in 5 patients: 4 in the R-CHOP-14 (6.6%) and 1 in the R-CHOP-21 cohort (2.6%), using triplex polymerase chain reaction (PCR) for PJ in bronchoalveolar fluid. None of the patients receiving P.jirovecii prophylaxis (n = 33) developed PJP, compared with 6.6% of those treated with R-CHOP-14 without such prophylaxis. An older age and R-CHOP administered every 14 rather than every 21 days increased the PJP risk. Trimethoprim/sulfamethoxazole prophylaxis is found to be highly efficient in preventing this life-threatening complication and, therefore, should be recommended for patients receiving the R-CHOP-14 regimen.

Outcome of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction in patients without human immunodeficiency virus infection.

BACKGROUND AND OBJECTIVE: Pneumonia caused by Pneumocystis jirovecii (PCP) in patients without human immunodeficiency virus (HIV) infection is associated with high mortality. The diagnosis of PCP at our institution is based on detection of DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to describe the clinical manifestations, outcomes and factors associated with mortality due to PCP, as diagnosed by PCR, in patients without HIV infection. METHODS: Over a 6-year period, all HIV-negative immunocompromised patients suspected of having an opportunistic pulmonary infection underwent diagnostic bronchoscopy. A multigene PCR assay that detects Pneumocystis jirovecii DNA was used for the diagnosis of PCP. Patients were considered to have PCP if they had underlying immunodeficiency, compatible signs and symptoms, abnormal radiological findings, and Pneumocystis jirovecii DNA was detected in a bronchoalveolar lavage fluid sample. Data was collected retrospectively. RESULTS: PCP was diagnosed in 58 patients. The underlying conditions included haematological malignancies (60.3%), solid tumours (17.2%) and immunosuppressive treatment (22.4%). The most common clinical features in patients with PCP were fever (94.6%), dyspnoea (67.2%) and cough (36.2%). The overall in-hospital mortality was 17.2% (10/58). Mortality was associated with co-infections, high lactate dehydrogenase levels, female gender, and higher pneumonia severity index and acute physiology and chronic health evaluation III scores. CONCLUSIONS: In this study, the mortality of HIV-negative patients with PCP was low compared with previous reports. We hypothesize that this finding resulted from the increased sensitivity of a PCR-based assay, as compared with traditional methods, for the diagnosis of PCP in HIV-negative patients.

Characterization of pulmonary venous hypertension patients with reactive pulmonary hypertension as compared to proportional pulmonary hypertension.

BACKGROUND: Patients with pulmonary venous hypertension (PVH) secondary to left heart disease can be further classified according to their hemodynamic profile: pulmonary hypertension (PH) in proportion to the pulmonary capillary wedge pressure (PCWP) and PH out of proportion to the PCWP or reactive PH. Currently, there are no measures that enable prediction of the development of reactive PH in patients with left heart disease. OBJECTIVES: In this study, we aim to characterize PVH patients with reactive PH as compared to proportional PH in an attempt to create a distinct profile for patients with left heart disease carrying a high risk for the development of reactive PH. METHODS: Thirty-three PVH patients with reactive PH and 29 PVH patients with proportional PH were analyzed retrospectively over a 6-year period. Clinical, laboratory, echocardiographic and hemodynamic parameters were noted and compared between subgroups. RESULTS: There was no significant difference between PVH patients with reactive and proportional PH with regard to gender, age (65.91 ± 11.9 vs. 66.69 ± 10.5 years) and body surface area (1.89 ± 0.24 vs. 1.9 ± 0.23 m(2)). Prevalence of the metabolic syndrome components was similar in both groups. Interestingly, PCWP was similar in both groups, as were the structural and functional parameters of the left heart. CONCLUSIONS: PVH patients with reactive PH have a similar profile as patients with proportional PH; consequently, the evolution of reactive PH is unpredictable. Therefore, it is imperative that physicians maintain a high index of suspicion for the development of reactive PH even in the early stage of heart disease.

Preliminary prospective explanatory observation on the impact of 3-month steroid therapy on the objective measures of sleep-disordered breathing.

BACKGROUND: Excess endogenous steroids are a risk factor for obstructive sleep apnea (OSA). The role of exogenous steroids in this setup is not known. In this study, we prospectively looked at the consequences of a 3-month steroid treatment on the objective measures of sleep-disordered breathing. METHODS: Patients scheduled for long-term steroids treatment underwent two sleep studies, the first before initiation and the second after 3 months of steroid therapy. Their weight and neck girth were measured. Correlations between the changes in the body weight, neck girth, and cumulative steroids dose to apnea/hypopnea index (AHI) change were examined. A group of untreated mild OSA patients (n = 23) served as control. RESULTS: Seventeen patients, five males and 12 females, mean age 52.4 ± 12.6 years, were studied. Fifteen patients increased their mean AHI by 56% from 9.8 ± 11.8 to 15.4 ± 15.8, p = 0.004. This increment was significantly higher when compared to the control group. Body weight and neck girth changes and cumulative steroid dose were not correlated to the AHI increment (Spearman's correlation coefficient r = 0.18 and p = 0.49, r = -0.23 and p = 0.37, r = -0.17 and p = 0.51, respectively). CONCLUSIONS: We found that the objective measures of sleep-disordered breathing worsened after the 3-month steroid treatment. Future studies to define pertinent mechanisms and clinical relevance are warranted.

Idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension: can we be certain?

Idiopathic pulmonary arterial hypertension (IPAH) is an isolated small-vessel disease comprising vasoconstriction, remodeling and thrombosis of small pulmonary arteries. However, there is evidence that IPAH does not respect anatomic boundaries and might extend into large vessels such as large central thrombi. On the other hand, chronic thromboembolic pulmonary hypertension (CTEPH) represents a distinct category of pulmonary hypertension as it is thought to be due to an occlusion of the major pulmonary arteries following a thromboembolic event. However, it is currently evident that in most patients there is a concomitant small-vessel disease. The involvement of both small and large vessels in both IPAH and CTEPH, together with a high incidence of silent thromboembolic events, might create difficulties in identifying the true cause of pulmonary hypertension. An accurate diagnosis of the cause determines the management and prognosis. Patients with CTEPH can potentially be offered curative surgery in the form of pulmonary endarterectomy; however, oxygen, vasodilators, anticoagulation, and lung transplantation are more feasible options for IPAH.

Radiological features of Pneumocystis jirovecii Pneumonia in immunocompromised patients with and without AIDS.

The aim of this study was to compare chest computerized tomography (CT) findings of Pneumocystis jirovecii pneumonia (PCP) in immunocompromised patients with and without acquired immune deficiency syndrome (AIDS). Chest CT findings and clinical parameters of 38 consecutive immunocompromised patients, nine with AIDS and 29 with other causes of immunosuppression, were characterized and compared. PCP in patients without AIDS was diagnosed after a significantly shorter time interval from symptom onset: 8 +/- 6 vs. 18 +/- 1.0 days (p = 0.024). From a radiographic point of view, non-AIDS patients had a significantly higher proportion of diffuse ground glass lesions, 86 vs. 44% (p = 0.02), and a lower proportion of cystic lesions, 3 vs. 56% (p = 0.015). The two subgroups did not differ in smoking status and the number of pack-years. On multivariant analysis, only the presence of AIDS was found to be a risk factor for the formation of pulmonary cystic lesions. Different immune reactions to the parasite P. jirovecii in immunocompromised patients with and without AIDS results in a different time lag between symptoms and a correspondingly different radiographic pattern: widespread ground glass opacities in the former and cystic lesions in the latter.

The response to bronchodilators in adults is not predictive of bronchial-hyperreactivity.

BACKGROUND: In some subjects with suspected asthma who have normal spirometry, administration of bronchodilators (BD) improves expiratory flow rates. The predictive value of this phenomenon in adults is not known. OBJECTIVES: To evaluate the predictive value of the response to BD for bronchial hyper-responsiveness (BHR) using the metacholine challenge test (MCT). Patients and methods. The study population included 62 non-smoking adult patients (41.9% women) 29.5 +/- 15.5 years of age (range 18-64 years) with suspected asthma with normal spirometry that underwent MCT within 1 week. The response to BD (200 mu g inhaled salbutamol) was compared between subjects with positive and negative MCT using cutoff levels of provocative concentrations of metacholine causing a 20% decrease in forced expiratory volume in 1 second (FEV(1)) (PC(20)) of 4 and 8 mg/mL. RESULTS: Mean (+/- SD) baseline FEV(1) was 87.8 +/- 12% of predicted. After BD administration the mean FEV(1) increased by 4.3 +/- 3.9%. The prevalence of BHR was 17.7% and 25.8% for PC(20) for PC(20) of 4 mg/mL and 8 mg/mL, respectively. The post-BD FEV(1) increment for subjects with positive and negative MCT tests was 3.9% +/- 3.3% versus 4.4% +/- 4.1%, respectively; p = 0.89, using cutoff of 4 mg/mL. The corresponding figures for cutoff of 8 mg/ml were 4.3% +/- 3.1% vs. 4.3% +/- 4.2%, respectively; p = 0.8465. There was no correlation between post-BD FEV(1) increment and PC(20) values in patients with positive MCT test for the above-mentioned cutoff levels (correlation coefficient r = 0.1645, p = 0.6289; and r = 0.2417, p = 0.4051, respectively). CONCLUSIONS: In adults with suspected asthma who have normal spirometry, the response to BD cannot be used to predict BHR.