Accelerated decline of lung function in COPD patients with chronic hepatitis C virus infection: a preliminary study based on small numbers of patients

STUDY OBJECTIVES: It has been suggested that chronic viral infection may increase the risk for development of COPD. This prospective study was designed to determine that chronic hepatitis C virus (HCV) infection is associated with accelerated decline of lung function in patients with COPD, and that antiviral therapy against HCV is effective for such patients. DESIGN: Prospective 5-year follow-up study. SETTING: University hospital. PATIENTS: Fifty-nine patients with COPD (group A, 15 HCV-negative ex-smokers; group B, 14 HCV-negative current smokers; group C, 14 HCV-positive ex-smokers; group D, 16 HCV-positive current smokers). INTERVENTIONS: After a 5-year follow-up period, 21 HCV-positive patients received interferon (IFN)-alpha therapy. Measurements and results: The rate of annual decline in FEV(1) and diffusing capacity of the lung for carbon monoxide (DLCO) during the 5-year follow-up period were significantly higher in group B (DeltaFEV(1), 59.7 mL/yr [SD, 17.5], p = 0.0008; DeltaDLCO, 3.50%/yr [SD, 0.44], p < 0.0001) and group C (DeltaFEV(1), 54.0 mL/yr [SD, 15.3], p = 0.0128; DeltaDLCO, 3.36%/yr [SD, 0.28], p < 0.0001) than in group A (DeltaFEV(1), 33.5 mL/yr [SD, 7.7]; DeltaDLCO, 2.66%/yr [SD, 0.34]). Moreover, these parameters in group D (DeltaFEV(1), 79.5 mL/yr [SD, 20.6]; DLCO, 4.5%/yr [SD, 0.40]) were also significantly higher than those in group B and group C. We evaluated the DeltaFEV(1) after IFN therapy during the 3-year follow-up period in the 8 IFN responders and 13 IFN nonresponders. DeltaFEV(1) in the IFN nonresponders did not significantly change during the 3-year follow-up period (before, 65.5 mL/yr [SD, 23.5]; after, 66.1 mL/yr [SD, 24.0]). However, DeltaFEV(1) in the IFN responders significantly decreased (before, 68.4 mL/yr [SD, 26.2]; after, 57.3 mL/yr [SD, 23.6], p = 0.0116). CONCLUSIONS: Our findings suggest that chronic HCV infection might accelerate decline in lung function in patients who already have COPD.     

Accelerated decline in lung function and impaired reversibility with salbutamol in asthmatic patients with chronic hepatitis C virus infection: a 6-year follow-up study

PURPOSE: Chronic hepatitis C virus (HCV) infection may have adverse effects on pulmonary function in patients with chronic obstructive pulmonary disease. This prospective study was designed to determine whether chronic HCV infection affects decline in lung function and airway responses to salbutamol in asthmatic patients. METHODS: Interferon alpha (6 MIU three times a week for 6 months) was given to 55 HCV-positive asthmatic patients, 18 of whom had a virologic response to interferon. Pre- and postbronchodilator forced expiratory volume in 1 second (FEV(1)) and reversibility with salbutamol or oxitropium at years 1, 3, and 6 after interferon therapy were examined. RESULTS: We found a significant decrease in pre- and postbronchodilator FEV(1) from year 1 to years 3 and 6 only in interferon nonresponders. Reversibility with salbutamol at years 3 and 6 was significantly lower in interferon nonresponders than in HCV-negative patients (P <0.0001) and interferon responders (P <0.0001). Moreover, there was a steep decline in reversibility with salbutamol during the follow-up period only in interferon nonresponders. In contrast, reversibility with oxitropium at years 3 and 6 was significantly higher in interferon nonresponders than in HCV-negative patients and interferon responders, and there was a steep increase in reversibility with oxitropium only in interferon nonresponders. In addition, declines in the diffusing capacity of the lung for carbon monoxide during follow-up were significantly greater in interferon nonresponders than in HCV-negative patients and interferon responders. CONCLUSION: Chronic HCV infection is associated with an accelerated decline in lung function and impaired reversibility with salbutamol among asthmatic patients who do not respond to interferon therapy.     

Interferon therapy of Turkish patients with chronic hepatitis B virus infection

BACKGROUND/AIMS: The efficacy of alpha interferon therapy in Turkish individuals with chronic hepatitis B virus infection was examined. METHODOLOGY: Sixty-one patients (54 males and 7 females) were studied between 1992 and 1996. Their mean age was 33.4 years (range: 20-57). Each was treated with 4.5 million international units interferon alpha 3 times a week for 24 weeks. Serum alanine aminotransferase (ALT) levels and hepatitis B virus markers (HBsAg, HBeAg, anti-HBe, and HBV DNA) were monitored. A liver biopsy was obtained before and 6 months after the termination of interferon therapy. RESULTS: Before treatment, the serum ALT level was elevated in all 61 subjects. Six months after the termination of therapy, 23 (38%) had a normal serum ALT level. In all patients, before the start of therapy and 6 months after the termination of therapy, HBsAg was detectable. In 36 (59%), HBeAg was present and anti-HBe was not detectable in serum before the initiation of therapy. In 12 (33%), the serum was negative for HBeAg and positive for anti-HBe 6 months after the termination of therapy. HBV DNA was detectable in all serum samples before the onset of therapy and disappeared in 14 (23%) patients, and continued to be undetectable 6 months after the termination of interferon therapy. Histological improvement defined by an improvement in the Knodell score of 2 points or more was observed in 38 (62%). CONCLUSIONS: Interferon therapy eliminates serum markers of active hepatitis B virus infection (eAg and HBV DNA) and is associated with histological improvement in 30-60% of Turkish patients with chronic HBV infection. Interferon therapy did not eliminate sAg from the serum and the histologic improvement achieved was often incomplete.     

Interferon and thymosin combination therapy in naive patients with chronic hepatitis C: preliminary results

Abstract: Aims/Background: This randomized study was performed to compare the efficacy of interferon-alpha (IFN-α) + thymosin alpha 1 (Tα1) treatment to that of IFN-α alone in light of biochemical and virological response of naive patients with chronic hepatitis C. Methods: Seventeen patients were treated with IFN α-2b (3 million units MU three times a week) + Tα1 (1 mg twice weekly); the other 17 patients received only IFN α-2b at the same dose. All patients were treated for 6 months and followed up for 12 months. Biochemical (ALT values) and virological (HCV-RNA) responses to treatment were determined. Results: Combination therapy showed significantly higher efficacy than monotherapy in achieving biochemical and virologic end-of-treatment response (p<0.05). At 12 month follow-up, the sustained biochemical response was slightly greater in patients treated with combination therapy than in those treated with monotherapy. No significant difference in response by HCV-1b subtype was observed between the two treatment groups; however, HCV-2c subtype showed a trend to responding better to IFN-α+Tα1 than to IFN-α alone. Conclusions: These data suggest that the immune modulator Tα1 may be additive or synergistic with IFN-α in normalizing end-treatment biochemical and virological responses in patients with chronic hepatitis C. Higher doses and/or more prolonged courses may improve the sustained response rates to this treatment.     

Increased responses to inhaled oxitropium bromide in asthmatic patients with active hepatitis C virus infection

STUDY OBJECTIVES: The interaction between chronic hepatitis C virus (HCV) infection and bronchial asthma is of considerable interest. This study was designed to examine whether differences in airway responses to an inhaled anticholinergic agent exist between asthmatic patients with and without active HCV infection. DESIGN: Controlled cross-sectional analysis. SETTING: University hospital. PATIENTS: Sixteen HCV-negative asthmatic patients and 36 HCV-positive asthmatic patients. INTERVENTIONS: All HCV-positive patients received interferon (INF) therapy for 6 months (INF responders, 16 patients; INF nonresponders, 20 patients). No patient had received INF within 3 years of the start of the study. MEASUREMENTS AND RESULTS: Airway hyperreactivity to methacholine (ie, the provocative concentration of methacholine causing a 20% fall in FEV(1) [PC(20)]), maximal increase in FEV(1), and forced expiratory flow between 25% and 75% of FVC (FEF(25-75)) after the administration of oxitropium bromide (200 micro g) were examined. At the start of the study, the groups were well-matched with respect to age, body mass index, and baseline lung function, including methacholine PC(20). The mean (SD) increase in FEV(1) after oxitropium bromide administration was significantly greater in patients with active HCV (95 [7] mL) than in HCV-negative asthmatic patients (68 [12] mL) and asthmatic patients with inactive HCV infection (69 [6] mL; p < 0.001). The increase in FEF(25-75) after oxitropium bromide administration was also significantly greater (250 [90] mL/s vs 170 [90] and 180 [80] mL/s, respectively; p < 0.029). CONCLUSIONS: In patients with asthma, active HCV infection is associated with increased bronchodilator responses to inhaled oxitropium bromide. HCV infection may modulate acetylcholine-mediated airway tone.     

Increased risk of nontuberculous mycobacterial infection in asthmatic patients using long-term inhaled corticosteroid therapy

Background and objective: The risk of pneumonia is increased among COPD patients using inhaled corticosteroids (ICS). However, there is uncertainty regarding the association between long‐term use of ICS and exacerbations of respiratory tract infections among asthmatic patients. Methods: A case‐control nested cohort study was performed to assess the association of asthma with nontuberculous mycobacterium (NTM) infection. Results: Among this cohort of 464 asthmatic patients, 14 experienced complications due to NTM infections, of which eight were caused by Mycobacterium avium‐intracellulare complex, three by M. kansasii, one by M. terrae and the remaining two by unclassifiable scotochromogens. Asthmatic patients with NTM infections were older (67.1 ± 8.6 vs 58.8 ± 12.3 years, P < 0.01) and had more severe airflow limitation (FEV₁%, 60.6 ± 10.3 vs 72.3 ± 18.3, P < 0.03) than those without NTM infections. All except one had received ICS treatment for more than 5 years, and 12 of the 14 patients used inhaled fluticasone propionate daily (four patients at a dose of 400 µg/day and eight patients at a dose >800 µg/day). Conclusions: These findings suggest that the risk of NTM infection may be greater in asthmatic patients who are older, have more severe airflow limitation and receive higher doses of ICS therapy.     

Interferon alfa therapy in patients with chronic hepatitis B virus infection. Effects on hepatitis B virus DNA in the liver

Pretrial and posttrial liver biopsy samples from 124 adult patients who participated in two randomized, controlled trials of interferon alfa therapy for chronic hepatitis B virus (HBV) infection were analyzed to determine the effects of interferon on the replication of HBV in the liver. Replicative forms of HBV DNA were detected in the pretrial biopsy samples from all and posttrial biopsy samples from 74% treated patients and 86% controls. Replicative forms of HBV DNA were detected in the posttrial biopsy samples from all patients who remained positive for hepatitis B e antigen and HBV DNA in the serum, in 77% treated patients and 80% controls who cleared HBV DNA in the serum but who remained positive for hepatitis B e antigen, but in only 19% treated patients and 40% controls who cleared HBV DNA as well as hepatitis B e antigen in the serum. Serum alanine aminotransferase levels were significantly lower in patients whose posttrial biopsies did not contain replicative forms of HBV DNA. In summary, we demonstrated that in most patients with chronic HBV infection treated with interferon alfa, serological response was associated with the disappearance of replicative forms of HBV DNA in the liver.     

Interferon alpha therapy in haemophilic patients with chronic hepatitis C: a French multicentre pilot study of 58 patients

BACKGROUND AND OBJECTIVES: Information about the long-term efficacy of interferon alpha (interferon-alpha) in haemophilic patients with chronic hepatitis not co-infected with the human immunodeficiency virus (HIV-1) is still limited. Previous studies seemed to indicate a low rate of response. The aim of this study was to evaluate the safety and long-term efficacy of interferon treatment in multi-transfused haemophiliacs. METHODS: Fifty-eight haemophiliacs were scheduled to receive 3 MU of interferon-alpha 2b three times a week for 12 months. The patients were followed up for at least 24 months post-treatment. Response was assessed by measurements of serum hepatitis C virus (HCV) RNA. RESULTS: Twenty-four patients (41.4%) dropped out. Except for seven patients, the symptoms that led to interrupting interferon treatment would probably not have resulted in the same decision in non-haemophilic patients. One patient developed an inhibitor to the deficient clotting factor without haemorrhagic consequences. In an intent to treat, the sustained virological response rate was 14%. However, when considering only the 34 patients who received the full treatment, HCV-RNA was cleared in eight patients (23%). CONCLUSIONS: This study suggests that multi-transfused haemophiliacs with chronic hepatitis not co-infected with HIV-1 respond to prolonged treatment with interferon-alpha in a similar proportion to that observed in non-haemophiliacs. There was a high rate of patients who did not complete the interferon-alpha treatment, and this seems to be characteristic of this patient population.     

Response-guided therapy for patients with hepatitis C virus genotype 6 infection: a pilot study

Summary. The optimal duration of treatment with pegylated interferon (PEG‐IFN) plus ribavirin (RBV) in patients with hepatitis C virus (HCV) genotype 6 is unknown. This study was aimed at determining treatment response on the basis of rapid virological response (RVR) of HCV genotype 6 in comparison with genotypes 1 and 3. Sixty‐six treatment naïve patients were treated with PEG‐IFN‐α2a (180 μg/week) plus weight‐based RBV (1000–1200 mg/day). Patients with genotype 1 n = 16) and genotype 3 (n = 16) were treated for a fixed duration of 48 and 24 weeks, respectively. Patients with genotype 6 (n = 34) who achieved RVR were treated for 24 weeks (response‐guided therapy) and the remaining patients were treated for 48 weeks (standard therapy). The mean baseline HCV RNA levels were not statistically different between groups (6.4 ± 0.8, 6.0 ± 1.0 and 6.5 ± 0.8 Log₁₀ IU/mL for genotypes 1, 3 and 6, respectively). Patients with genotypes 1, 3 and 6 achieved RVR in 43.8%, 87.5% and 73.5% of cases, respectively. One patient with genotype 1 and 3 with genotype 6 were considered nonresponders and discontinued therapy. Sustained virological response (SVR) was achieved in 62.5%, 81.3% and 76.5% of patients with genotypes 1, 3 and 6, respectively. The SVR rate in patients with genotype 6 who underwent response‐guided therapy was 88%. This pilot study suggested that the SVR rate of HCV genotype 6 was at an intermediate level between those of genotypes 3 and 1. Treatment with PEG‐IFN plus RBV for 24 weeks may be sufficient for patients with genotype 6 who achieve RVR. Prospective randomized trials are required to evaluate this response‐guided strategy in a larger number of patients with genotype 6.     

Immunogenicity of recombinant hepatitis B virus vaccine in patients with and without chronic hepatitis C virus infection： A case-control study

AIM： To compare the response of standard hepatitis B virus （HBV） vaccination between patients with chronic hepatitis C virus （HCV） infection and healthy individuals. METHODS： This is a prospective case-control study. A total of 38 patients with chronic HCV infection and 40 healthy controls were included. Vaccination was performed by injection of 20μg recombinant HBsAg into the deltoid muscle at mo 0,1 and 6. Anti-HBs concentration was determined 3 mo after the last dose and compared between the two groups. The response pattern was characterized as （1） high-response when the anti-HBs antibody titer was 〉 100 IU/L, （2） low-response when the titer was 10-100 IU/L. and （3） no-response when the titer was 〈 10 IU/L. RESULTS： In the patient group, there were 10/38 （26.3%） non-responders, 8/38 （21.1%） Iow-responders and 20/38 （52.6%） high-responders. The corresponding values in the control group were 2/40 （5.0%）, 7/40 （17.5%） and 31/40 （77.5%）, respectively. The response pattern was statistically different between the two groups. In multivariate analysis, smoking was a significant confounder, while HCV infection lost its significant correlation with lower antibody response. CONCLUSION： Patients with chronic HCV infection tend to respond weakly to HBV vaccination compared to healthy individuals, though this correlation is not independent according to multivariate analysis.     

Renal involvement in patients with chronic hepatitis C virus infection

There is an increasing recognition of the association between chronic hepatitis C virus (HCV) infection and glomerular diseases. Renal complications may be the presenting manifestation of HCV infection. Patients may present with systemic vasculitis secondary to cryoglobulinemia, or they may present with proteinuria, microscopic hematuria, acute renal failure, or nephrotic syndrome. The pathogenesis of HCV-associated renal disease remains incompletely understood; however, deposition of HCV-containing circulating immune complexes in the glomeruli (ie, subendothelial space and mesangium) seems to play an important role. The most common renal pathology associated with HCV infection is type I membranoproliferative glomerulonephritis with or without cryoglobulinemia. In patients who do not have significant renal impairment, combination therapy with interferon-á and ribavirin is the treatment of choice. The experience with this combination therapy is quite limited in patients with renal impairment. Prolonged courses of high-dose interferon-á therapy have been successfully used for these patients; however, relapse of HCV viremia and recurrence of renal disease is common after discontinuation of therapy.     

Extrahepatic manifestations in patients with chronic hepatitis C virus infection

PURPOSE OF REVIEW: Chronic hepatitis C virus infection often has autoimmune clinical and analytic features. This review analyzes recent data on the close association of chronic hepatitis C virus infection with autoimmune and lymphoproliferative processes. RECENT FINDINGS: Hepatitis C virus infection has been associated with both organ-specific (thyroiditis, diabetes) and systemic autoimmune diseases. Experimental, virologic, and clinical evidence has demonstrated a close association between hepatitis C virus infection and Sj?gren syndrome, with hepatitis C virus-associated Sj?gren syndrome being indistinguishable in most cases from the primary form. With respect to rheumatoid arthritis, patients with hepatitis C virus-related polyarthritis and positive rheumatoid factor may fulfill the classification criteria for rheumatoid arthritis. Hepatitis C virus has also been associated with an atypical presentation of antiphospholipid syndrome, as well as with the development of sarcoidosis. A higher prevalence of hematologic processes in patients with hepatitis C virus infection has recently been reported, including cytopenias and lymphoproliferative disorders. Recent data are available on the use of new immunosuppressive and biologic agents (mainly mycophenolate mofetil, anti-tumor necrosis factor agents, and rituximab) in patients with hepatitis C virus infection and autoimmune or lymphoproliferative manifestations. SUMMARY: There is increasing evidence of a close association of hepatitis C virus infection with autoimmune and hematologic processes. The sialotropism of hepatitis C virus may explain the close association with Sj?gren syndrome, and its lymphotropism links the virus to cryoglobulinemia, autoimmune cytopenias, and lymphoma. The substantial overlap between cryoglobulinemic features and the classification criteria for some systemic autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, and polyarteritis nodosa) make the differentiation between mimicking and coexistence difficult.     

Erectile dysfunction in patients with chronic hepatitis C virus infection

Background and study aimsHepatitis C virus (HCV) infection is a major public health problem worldwide and in Egypt. Several studies have suggested that chronic HCV infection may be associated with erectile dysfunction (ED) in men. The aim of our study was to detect the prevalence of ED among male patients with chronic HCV infection.Patients and methodsThe study included 150 male patients with chronic HCV infection (124 patients with chronic hepatitis and 26 patients with HCV-associated liver cirrhosis). The Child–Pugh score was used to assess the severity of cirrhosis. An Arabic validated version of the five-item International Index of Erectile Function (IIEF-5) was used to detect the presence and severity of ED.ResultsThe patients’ age ranged from 20 to 80 years with mean age ± standard deviation (SD; 50 ± 17.19) years. The prevalence of ED among patients with chronic HCV infection was found to be 29.3%. The prevalence was significantly higher in cirrhotic as compared to chronic hepatitis patients (p < 0.001) and the average ED score was significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. There was a highly significant relation between the severity of ED and the severity of liver disease. There was a significant negative correlation between serum bilirubin and ED score and a significant positive correlation between serum albumin and ED score in patients with liver cirrhosis.ConclusionAbout 30% of patients with chronic HCV infection were found to have ED; so, given the high prevalence of HCV infection in Egypt, chronic HCV infection may be considered in the differential diagnosis of ED. There was a highly significant relation between the severity of ED and the severity of liver disease and the majority of patients with liver cirrhosis proved to be suffering from ED, which may be related to the associated hypoalbuminaemia.     

Reversible autonomic dysfunction during antiviral treatment in patients with chronic hepatitis C virus infection: Anti-HCV therapy and autonomic function

Background

The first clinical sign of chronic hepatitis C virus (HCV) infection can be one of the various extrahepatic manifestations. During antiviral treatment, symptoms of HCV-associated neuropathies usually improve, but can also worsen and lead to discontinuation of anti-HCV therapy. Recently, we have reported autonomic dysfunction in patients with HCV infection.

Objectives

In the present prospective study, we analyzed the changes of autonomic function during anti-HCV treatment.

Patients and Methods

Cardiovagal autonomic function was assessed in 22 HCV RNA-positive, treatment-naive patients by determining heart rate variability (HRV) and baroreflex sensitivity (BRS), at the beginning of treatment and 12, 24 and 48 weeks of antiviral therapy. interferon alfa-2 and ribavirin were given according to the guidelines.

Results

Both HRV and BRS time and frequency domain indices decreased after 12 weeks of therapy compared to the pre-treatment values; then the mean±SD values increased significantly by week 24 and continued to improve by week 48 of therapy-253.0±156.1 ms before therapy vs 111.6±81.9 at week 12, and 183.4±169.6 at week 24 vs 211.6±149.1 ms at week 48 for low-frequency HRV index; p<0.05 for all comparisons). These changes were independent from the presence of cryoglobulins and from virologic response.

Conclusions

The first rise followed by reversible autonomic dysfunction during antiviral therapy may be caused by the immunomodulatory actions of interferon alfa-2.     

慢性HBV/HCV感染人群伴随的免疫相关表现

慢性HBV/HCV感染者常常伴有自身免疫系统紊乱,在丙型肝炎中尤为常见。介绍了慢性丙型肝炎患者免疫状态紊乱的机制,出现非器官特异性自身抗体的比例,以及伴随的免疫相关疾病,如混合型冷球蛋白血症、肾小球肾炎、干燥综合征、甲状腺疾病、2型糖尿病的临床表现、诊断和治疗等。简述了慢性乙型肝炎患者免疫状态紊乱的机制、相关的免疫表现以及抗病毒治疗对其的影响。慢性乙型或丙型肝炎的抗病毒治疗可以减轻伴随的免疫系统疾病,但是不宜采用干扰素治疗,因此,乙型肝炎患者应采用核苷和核苷酸类药物治疗,丙型肝炎患者应采用直接抗病毒药物治疗。     

Iron overload in patients with chronic hepatitis C virus infection: clinical and histological study

BACKGROUND: Recently it has been found that iron is an important element in the natural history of hepatitis C. Serum markers of iron stores are frequently increased in chronic hepatitis C virus (HCV)-infected carriers but the real impact of the hepatic iron overload is poorly understood. The purpose of the present paper was to determine the prevalence of iron overload and to study the relationship between hepatic iron concentration (HIC) and clinical, biochemical and histological characteristics in chronic HCV-infected carriers. METHODS: Patients presenting with anti-HCV and HCV-RNA were included. Hepatic iron concentration was determined in liver tissue by atomic absorption spectrophotometry. The association between HIC and age, gender, risk factor of transmission, duration of infection, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, iron and serum ferritin, transferrin saturation, HCV-RNA level, grading of inflammatory activity, staging of fibrosis, hepatic steatosis, and stainable iron was analyzed. Statistical analysis included the Mann-Whitney test and a multiple linear regression model. RESULTS: Ninety-six patients (58% male) with a mean age of 44 +/- 10 years were studied. Serum iron, ferritin and transferrin saturation were elevated in 28%, 27% and 12.5% of patients, respectively. Stainable iron was detected in few patients (15.6%). Higher grades of stainable iron (2 and 3) were observed in only 7%. The HIC (>30 mmol/g dry weight) was elevated in five patients (5%). Neither grading nor staging were related to HIC. Higher HIC were observed in male patients (P < 0.001), in patients with elevated serum ferritin (P = 0.001) and in patients with stainable iron (grades 2 and 3; P = 0.001). Multiple linear regression analysis showed that only stainable iron was independently correlated with HIC (P = 0.003). CONCLUSIONS: Iron overload in chronically HCV-infected patients was uncommon and hepatic iron content seemed not to be related to the liver damage process. In the eventuality of iron overload, histochemical liver iron is a useful marker to estimate HIC.     

Lung function in school-aged asthmatic children with inhaled cromoglycate, nedocromil and corticosteroid therapy.

Two-thirds of the children with asthma in our area use cromones and only one-third steroids as the maintenance therapy. This study aimed to evaluate our treatment policy based on the international consensus. Peak expiratory flow (PEF), dynamic spirometry and bronchodilation test results were therefore collected in 195 school-aged patients who visited our outpatient clinic in 1995. Sixty-four children (33%) used cromoglycate, 86 (44%) nedocromil and 45 (23%) inhaled steroids. Twenty-five (12%) needed combination therapy, mainly with salmeterol. Lung function results were good, and there were no significant differences between the therapeutic groups irrespective of whether pre- or postbronchodilator values were considered. PEF was decreased in eight (4%), forced expiratory volume in one second (FEVI) in four (2%) and maximum mid-expiratory flow (MMEF) in 33 (17%) patients. At least one result was decreased in 39 (20%) cases, in most cases (77%) MMEF alone. Significant rises after salbutamol inhalations were observed in 17 (9%) in PEF, in two (1%) in FEV1 and 20 (10%) in MMEF values. Thus, the bronchodilation test was positive in 33 (17%) cases, and in 22 (11%) cases it was the only sign of bronchial obstruction. Over 70% of the children with asthma can be treated with cromones by a stepwise treatment modality. Inhaled steroids can be restricted to those not controllable by cromones. Lung function tests, including postbronchodilator values, should be part of the follow-up of continuous maintenance medication for asthma.