[A female with expiratory wheezing and inspiratory stridor]. / Een vrouw met in- en expiratoir piepende ademhaling.

A 42-year-old woman was seen with an inspiratory stridor and expiratory wheezing. The wheezing responded quickly to asthma treatment. The stridor, however, was caused by a significant narrowing of the trachea between the branching of a tracheal bronchus ('bronchus suis' or ' pig bronchus') and the main carina.

Comparison of eNO and histamine hyperresponsiveness in diagnosing asthma in new referrals.

The mainstay of the diagnosis of asthma is the presence of reversible airway obstruction. Exhaled NO levels are increased in asthma, in close relationship with the amount of airway inflammation, and may be used for monitoring the disease and adjusting therapy. In this study we investigated the role of eNO as a diagnostic for asthma, compared with the FEV1-reversibility and the PC20 (20% decrease of the FEV1 in the bronchial histamine provocation test), in two independent centers, on an unselected population. ENO measurements were performed with chemoluminesence technique in one center and with an electrochemical device in the other. Only after correction for so-called nuisance factors (allergy, use of inhaled steroids, recent infection, smoking, sex and the use of nitrate food) the eNO appeared as a diagnostic with equal power as the FEV1-reversibility and the PC20. Therefore, screening for asthma in our study population, with the eNO measurement, is a simple, fast and safe strategy.

Nitric oxide diffusing capacity versus spirometry in the early diagnosis of emphysema in smokers.

The diffusion capacity for nitric oxide (DLNO) is independent of pulmonary capillary blood volume and equals the membrane diffusing capacity. Therefore the DLNO could be more sensitive in detecting alveolar destruction than the DLCO. We measured flow-volumes curves, DLNO, DLCO, the transfer coefficients KNO (DLNO/VA) and KCO (DLCO/VA) and performed computed tomography (CT) scans in 263 randomly selected heavy smokers. Subjects with areas > or =1% of the total lung volume showing an attenuation <-950 Hounsfield Units were considered to have emphysema. In 36 subjects emphysema was diagnosed with CT, a low KNO was present in 94 subjects, and in 95 subjects a FEV1/FVC ratio <70% was seen. The area under the ROC curve for detection CT-based emphysema was 0.894 for the KNO, 0.822 for the KCO and 0.795 for FEV1/FVC, meaning that the KNO has a slightly higher sensitivity to detect emphysema than the KCO and FEV1/FVC. The positive predictive value of KNO however was low (34.7%), while the negative predictive value of KNO was very high (98.2%), indicating an emphysema exclusion test. The DLNO/DLCO ratio is significantly higher in the study group compared to normal subjects.

Pattern of diffusion disturbance related to clinical diagnosis: The K(CO) has no diagnostic value next to the DL(CO).

AIM OF THE STUDY: The diffusion capacity of the lung for carbon monoxide (DL(CO)) is an important tool in the diagnosis and follow-up of patients with pulmonary diseases. In case of a decreased DL(CO) the K(CO), defined as DL(CO)/V(A) (V(A) is alveolar volume), can differentiate between normal alveolocapillary membrane (normal K(CO)) and abnormal alveolocapillary membrane (low K(CO)). The latter category consists of decreased surface of the membrane, increased thickness or decreased perfusion of ventilated alveoli. The V(A)/TLC (TLC is total lung capacity determined by whole body plethysmography) can partially differentiate between these categories. The aim of this study was to investigate the diagnostic value of the specific diffusion disturbances, which can be constructed by combining the DL(CO), K(CO) and V(A)/TLC. METHODS: In 460 patients the diagnosis made by clinicians were fitted into five diagnostic categories: asthma, chronic obstructive pulmonary disease (COPD), treatment effects of haematologic malignancies, heart failure and diffuse parenchymal lung diseases (DPLD). These categories were linked to the pattern of diffusion disturbance. RESULTS: Almost all patients with asthma have a normal DL(CO), most patients in the other groups do not have the expected pattern of diffusion disturbance, especially in the group with DPLD a bad match is observed. CONCLUSION: In this study the pattern of diffusion disturbance is of limited use in establishing a diagnosis. The use of the K(CO) next to the DL(CO) has no additional diagnostic value. Regional ventilation-perfusion inequality probably forms an important underlying mechanism of decreased DL(CO).

Alveolar volume determined by single-breath helium dilution correlates with the high-resolution computed tomography-derived nonemphysematous lung volume.

BACKGROUND: The alveolar volume (V(A)), determined by single-breath helium dilution, is a measure for the total lung capacity (TLC) that is very sensitive to ventilatory disturbances. In chronic obstructive pulmonary disease (COPD), the emphysematous lung parts are less accessible to test gas; therefore, the V(A) is smaller than TLC measured by multiple-breath helium dilution (TLC(He)). OBJECTIVES: The aim of this study was to investigate whether the V(A) represents the nonemphysematous lung parts. METHODS: We measured V(A) as part of the diffusing capacity for carbon monoxide (DL(CO)), TLC(He) and spirometry in 50 patients with COPD. High-resolution computed tomography (HRCT) scans of all subjects were analyzed with the density mask method, where parts with an attenuation of less than -950 Hounsfield units were considered as emphysematous. RESULTS: A strong correlation was observed between the V(A) (mean 5.2 liters) and nonemphysematous HRCT lung volume (mean 5.2 liters, r(2) = 0.9) and between the TLC(He) (mean 6.6 liters) and total HRCT lung volume (mean 6.4 liters, r(2) = 0.9). Bland-Altman plots showed considerable disagreement between the V(A) and the nonemphysematous HRCT lung volume. A weak correlation between the forced expiratory volume in 1 s (mean 46% predicted) and DL(CO) (mean 46% predicted) versus the HRCT emphysema ratio (nonemphysematous/total HRCT lung volume) was observed (r(2) = 0.3 and 0.3, respectively). CONCLUSION: We concluded that the V(A) correlates with the nonemphysematous HRCT lung volume, although the two measurements are not equivalent, possibly due to technical factors.

The effect of red cell transfusion on nitric oxide diffusing capacity.

BACKGROUND: The diffusion capacity of the lung for nitric oxide (DLNO) is supposed to reflect the properties of the alveolocapillary membrane better than the diffusion capacity of the lung for carbon monoxide (DLCO), due to a much stronger binding of NO to haemoglobin (Hb). OBJECTIVES: The aim of this study was to investigate the effect of Hb concentration on the DLNO. METHODS: The DLNO and DLCO (single-breath method) were measured in 10 anaemic patients before and shortly after red cell transfusion. RESULTS: The mean increase in Hb concentration was 2.6 g/dl. Whereas DLCO increased as predicted by the reference equations, the DLNO did not change: mean DLCO rose from 13.6 to 16.5 ml/min/mm Hg (increase of 122%), mean DLCO corrected for Hb rose from 18.8 to 19.3 ml/min/mm Hg (103%) and mean DLNO rose from 75.6 to 77.8 ml/min/mm Hg (103%). CONCLUSION: The DLNO is not influenced by Hb concentration.

Lung function changes and pulmonary complications in patients with stage III non-small cell lung cancer treated with gemcitabine/cisplatin as part of combined modality treatment.

INTRODUCTION: Lung cancer is the leading cause of cancer mortality. Chemotherapy, ideally a platinum-based regimen as part of combined modality treatment, is appropriate for selected patients with locally advanced stage III non-small cell lung cancer (NSCLC) who have a good performance status. However, chemotherapy can induce side effects including lung function changes. AIM OF THE STUDY: Retrospective analysis of lung function changes in 44 patients with stage III NSCLC treated with neoadjuvant chemotherapy (NCT) followed by surgery and/or radiotherapy. PATIENTS AND METHODS: NCT consisted of three cycles of gemcitabine/cisplatin. The following data were analysed: age, sex, the presence of chronic obstructive pulmonary disease (COPD), smoking behaviour, response, complications after surgery and/or radiotherapy, and VC, FEV(1), DL(co) and K(co) before and after chemotherapy. DL(co) values were corrected for haemoglobin concentrations. RESULTS: We found a significant decline of K(co) (-13.5% of pred; 95% CI: -16.6 to -10.4; P<0.0001), independent of tumor response or presence and severity of COPD. FEV(1) and FEV(1)/VC showed significant increases irrespective of tumor response. Significantly more pulmonary complications were recorded in the radiotherapy group after NCT (P=0.009) compared to patients who underwent surgical therapy after NCT. CONCLUSIONS: Patients diagnosed with NSCLC stadium III who were treated with NCT consisting of cisplatin and gemcitabine showed a significant decline of DL(co) and K(co), irrespective of tumor response, presence and severity of COPD, sex and number of cycles of chemotherapy. Significantly more pulmonary complications were seen in patients treated with NCT and radiotherapy compared with patients treated with NCT and surgery. Questions concering the pathophysiological mechanisms of lung function changes and long term follow-up of pulmonary toxicity due to NCT remain still unanswered and have to be subject of future studies.

Reduction of variability of exhaled nitric oxide in healthy volunteers.

Exhaled nitric oxide (eNO) is elevated in patients with asthma in contrast to healthy subjects, although the variability is high. In this study, we tried to reduce the variability of eNO in healthy subjects. We measured eNO using ERS guidelines with a fixed exhalation flow of 250 ml/s in 117 (72 women, 45 men) non-smoking healthy subjects and correlated this to antropometric data and standard lung function measurements. Using a model previously defined by Hyde et al., we selected parameters that were likely to have a high correlation with eNO. ENO was log-normally distributed. The normal values for eNO are significantly (P < 0.001) different for men and women: in women mean ln eNO levels (SD) were 1.49 (0.34), in men 1.74 (0.41) (back-transformed value 4.43 resp. 5.73 ppb). Using multiple regression analysis, only In D(m,CO), InTLC and In sG(aw) showed a significant positive correlation with In eNO in men, although only 20% of the variability of eNO could be explained. In women no correlation was observed and only 5% ofthe variability was explained. The high variability of eNO could only partly be explained in men, which makes the use of reference equations not very helpful.

Single-agent gemcitabine in patients with resistant small-cell lung cancer.

OBJECTIVE: This study was conducted to assess the activity and toxicity ofgemcitabine in patients with resistant small-cell lung cancer (SCLC). PATIENTS TAND METHODS: Forty-one patients with limited- or extensive-stage SCLC, who were previously treated with at least one chemotherapeutic regimen and progressed during or within three months of finishing the last regimen, were treated with 1000 mg/m2 gemcitabine on days 1, 8, and 15 of a four-week cycle. RESULTS: Thirty-eight patients were evaluable for response. Five partial and no complete responses were seen, for an overall response rate of 13% (95% confidence interval (CI): 6%-27%). Time to progression varied from 4 to 20 weeks, with a median of 8 weeks. Median survival was 17 weeks (range 4-84 weeks). Hematological toxicity mainly consisted of NCI-CTC grade 3 thrombocytopenia (29% of patients) and, to a lesser extent, grade 3 leukopenia (18% of patients). Non-hematological toxicity was mild, with nausea being the most commonly reported event. CONCLUSIONS: Gemcitabine has modest activity in patients with resistant SCLC. There is some non-cross resistance to most agents against SCLC.

Reference values for alveolar membrane diffusion capacity and pulmonary capillary blood volume.

The reference values for diffusion capacity of the alveolar capillary membrane (Tm,CO) and pulmonary capillary volume (Qc) are scarce, while the standard deviations of the equations are large. New equations and residual standard deviations (RSDs) were determined in a sample of healthy subjects. Tm,CO and Qc values were measured in 117 (72 females, 45 males) nonsmoking healthy subjects. The carbon monoxide transfer factor (TL,CO) was determined when the volunteer was breathing room air and subsequently, when the volunteer was breathing 100% oxygen. From these data, Tm,CO and Qc values were calculated. The females' TL,CO was 3.15 mmol x min(-1) x kPa(-1) lower than the males', apparently caused by lower female lung volume. Tm,CO and Qc were lower in females, but correction for lung volume eliminated this difference. Qc(-1) reference equations for females and males, respectively, are 4.375 x 10(-2) - 1.085 x l0(-2) x height and 4.455 x 10(-2) -1.085 x 10(-2) x height (RSD for both sexes: 2.544 x 10(-3)). Tm,CO(-1) reference equations for females and males, respectively, are 0.111+3.304 x 10(-4) x age-4.753 x 10(-2) x height and 0.127+3.304 x 10(-4) x age-4.753 x 10(-2) x height (RSD for both sexes: 1.085 x 10(-2)). The general character of these equations complies with earlier publications, the only difference being that the RSDs are 1.18-2.76 times lower. New reference equations for diffusion capacity of the alveolar capillary membrane and pulmonary capillary volume are available with considerably smaller residual standard deviations.

A patient with diabetes insipidus and periorbital swellings; Erdheim-Chester disease.

Erdheim-Chester disease is a rare multisystem disease in which a progressive xanthogranulomatous infiltration of several tissues can be seen. We describe a woman, known to have diabetes insipidus for ten years, with periorbital, retroperitoneal, mediastinal, axillar and inguinal involvement. On histological examination a granulomatous infiltration of fatty tissue and striated muscle was seen, consisting of Touton giant cells, histiocytes with foamy cytoplasm and lymphocytes. Immunohistochemical staining with CD-1a and S-100 was negative and on electron microscopy no Langerhans granules were seen. These findings led to the diagnosis of Erdheim-Chester disease. She had a good response on steroids. Because of some similar clinical features of Langerhans cell histiocytosis and Erdheim-Chester disease, a histiocyte disorder seems the most probable cause.

Hodgkin's disease presenting as a parasternal chest wall mass.

A 53 year-old Moroccan woman presented with a tender parasternal mass. Computerized tomography showed a mediastinal mass protruding through the sternum. Cytologic examination of fluid collected from the mass repeatedly showed acute inflammation. Tuberculostatics were started. Since patient did not improve on tuberculostatics, a small supraclavicular lymph node was removed. Histologic examination showed Morbus Hodgkin of the nodular sclerosing type. Ultimately, cytologic examination of fluid from the parasternal mass showed atypical cells. Response on chemotherapy was excellent with complete disappearance of the parasternal mass. This is a very unusual extranodal presentation of Hodgkin's disease.