Aspergillus serology and clinical outcomes in patients with bronchiectasis: data from the European Bronchiectasis Registry (EMBARC).

INTRODUCTION: Aspergillus sp. cause diverse clinical manifestations in bronchiectasis including Allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS) and raised IgG indicating exposure or infection with Aspergillus. RESEARCH QUESTION: What is the prevalence and clinical significance of Aspergillus-associated conditions in individuals with bronchiectasis? METHODS: Bronchiectasis patients enrolled into the EMBARC registry from 2015 to 2022 with laboratory testing for Aspergillus lung disease (total IgE, specific IgE to Aspergillus or Aspergillus skin test, IgG to Aspergillus and blood eosinophil counts) were included for analysis. Modified-ISHAM-ABPA working group criteria (2021) were used to define ABPA. RESULTS: 9953 patients were included. 608 (6.1%) were classified as having ABPA, 570 (5.7%) showed Aspergillus sensitization, 806 (8.1%) had raised Aspergillus-specific IgG without sensitisation, 184 (1.8%) were both sensitised to Aspergillus and had raised Aspergillus-specific IgG and 619 (6.2%) had eosinophilic bronchiectasis (elevated eosinophil counts without evidence of Aspergillus lung disease). The remaining 72.0% had negative Aspergillus serology. Patients with ABPA, Aspergillus sensitization, and raised Aspergillus-specific IgG had more severe disease, with worse lung function and more frequent exacerbations at baseline. During long-term follow-up, patients with raised Aspergillus-specific IgG had higher exacerbation frequency and more severe exacerbations. Aspergillus sensitization associated with increased exacerbations and hospitalisations only in patients not receiving inhaled corticosteroids. INTERPRETATION: Aspergillus lung disease is common in bronchiectasis. Raised IgG to Aspergillus is associated with significantly worse outcomes while ABPA and Aspergillus sensitization are associated with severe disease and exacerbations with a risk that is attenuated by inhaled corticosteroid use.

Efficacy and safety of Hizentra(®) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy.

A prospective, open-label, multicenter, single-arm, Phase III study evaluated the efficacy and safety of Hizentra(®), a 20% human IgG for subcutaneous administration, in 51 primary immunodeficiency patients over 40 weeks. Patients previously on intravenous or subcutaneous IgG were switched to weekly subcutaneous infusions of Hizentra(®) at doses equivalent to their previous treatment. IgG levels achieved with Hizentra(®) were similar to pre-study levels with subcutaneous, and higher by 17.7% than pre-study levels with intravenous IgG. No serious bacterial infections were reported in the efficacy period. The rate of all infections was 5.18/year/patient, the rates of days missed from work/school, and days spent in hospital were 8.00/year/patient and 3.48/year/patient, respectively. Local reactions (rate 0.060/infusion) were mostly mild (87.3%). No serious, Hizentra(®)-related adverse events were reported. Individual median infusion durations ranged between 1.14 and 1.27 h. Hizentra(®) maintained or improved serum IgG levels without dose increases and effectively protected patients against infections.

Bronchoscopic balloon dilatation in the management of bronchial stenosis following lung transplantation.

BACKGROUND: Bronchial stenosis (BS) is currently found in 7-15% of lung transplantation (LT) recipients. Current treatment strategies have included Nd:Yag laser, cryotherapy, bougie dilatation and stent placement. Bronchoscopic balloon dilatation has been used as alternative treatment in a few cases with controversial results. This is a study to prospectively assess the efficacy of bronchoscopic balloon dilatation as a first step in the management of post-LT BS. METHODS: From January 1995 to December 2002, bronchoscopic balloon dilatation was evaluated as first therapeutic option in all consecutive LT patients with BS. Symptoms, pulmonary function tests, airway diameter and use of other therapeutic techniques were evaluated. RESULTS: A total of 10 out of 284 anastomed airways (3.5%) in 9 out of 152 LT patients were included in the study and follow-up lasted from 6 to 81 months. Dilatation of all but one BS met with initial success: increase of both luminal dimensions and forced vital capacity (P=0.01), and relief of symptoms. Bronchoscopic balloon dilatation long-term follow-up showed effective results in 5 out of 10 (50%) bronchial stenoses, after an average of 4 bronchoscopic balloon dilatation procedures (range 1-8). No severe complications were observed. Stent placement was required in the other 5 bronchial stenoses. CONCLUSIONS: Bronchoscopic balloon dilatation is a safe method that should be considered as first therapeutic treatment of post-LT BS. Its use avoids the need for stent placement in up to 50% of cases.

Predicting high risk of exacerbations in bronchiectasis: the E-FACED score.

BACKGROUND: Although the FACED score has demonstrated a great prognostic capacity in bronchiectasis, it does not include the number or severity of exacerbations as a separate variable, which is important in the natural history of these patients. OBJECTIVE: Construction and external validation of a new index, the E-FACED, to evaluate the predictive capacity of exacerbations and mortality. METHODS: The new score was constructed on the basis of the complete cohort for the construction of the original FACED score, while the external validation was undertaken with six cohorts from three countries (Brazil, Argentina, and Chile). The main outcome was the number of annual exacerbations/hospitalizations, with all-cause and respiratory-related deaths as the secondary outcomes. A statistical evaluation comprised the relative weight and ideal cut-off point for the number or severity of the exacerbations and was incorporated into the FACED score (E-FACED). The results obtained after the application of FACED and E-FACED were compared in both the cohorts. RESULTS: A total of 1,470 patients with bronchiectasis (819 from the construction cohorts and 651 from the external validation cohorts) were followed up for 5 years after diagnosis. The best cut-off point was at least two exacerbations in the previous year (two additional points), meaning that the E-FACED has nine points of growing severity. E-FACED presented an excellent prognostic capacity for exacerbations (areas under the receiver operating characteristic curve: 0.82 for at least two exacerbations in 1 year and 0.87 for at least one hospitalization in 1 year) that was statistically better than that of the FACED score (0.72 and 0.78, P<0.05, respectively). The predictive capacities for all-cause and respiratory mortality were 0.87 and 0.86, respectively, with both being similar to those of the FACED. CONCLUSION: E-FACED score significantly increases the FACED capacity to predict future yearly exacerbations while maintaining the score's simplicity and prognostic capacity for death.

Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients.

Pseudomonas aeruginosa colonisation has a negative effect on pulmonary function in cystic fibrosis patients. The organism can only be eradicated in the early stage of colonisation, while reduction of bacterial density is desirable during chronic colonisation or exacerbations. Monthly, or at least 3-monthly, microbiological culture is advisable for patients without previous evidence of P. aeruginosa colonisation. Cultures should be performed at least every 2-3 months in patients with well-established colonisation, and always during exacerbations or hospitalisations. Treatment of patients following the first isolation of P. aeruginosa, but with no clinical signs of colonisation, should be with oral ciprofloxacin (15-20 mg/kg twice-daily for 3-4 weeks) plus inhaled tobramycin or colistin (intravenous treatment with or without inhaled treatment can be used as an alternative), while patients with acute infection should be treated for 14-21 days with high doses of two intravenous antimicrobial agents, with or without an inhaled treatment during or at the end of the intravenous treatment. Maintenance treatment after development of chronic P. aeruginosa infection/colonisation (pathogenic colonisation) in stable patients (aged>6 years) should be with inhaled tobramycin (300 mg twice-daily) in 28-day cycles (on-off) or, as an alternative, colistin (1-3 million units twice-daily). Colistin is also a possible choice for patients aged<6 years. Treatment can be completed with oral ciprofloxacin (3-4 weeks every 3-4 months) for patients with mild pulmonary symptoms, or intravenously (every 3-4 months) for those with severe symptoms or isolates with ciprofloxacin resistance. Moderate and serious exacerbations can be treated with intravenous ceftazidime (50-70 mg/kg three-times-daily) or cefepime (50 mg/kg three-times-daily) plus tobramycin (5-10 mg/kg every 24 h) or amikacin (20-30 mg/kg every 24 h) for 2-3 weeks. Oral ciprofloxacin is recommended for patients with mild pulmonary disease. If multiresistant P. aeruginosa is isolated, antimicrobial agents that retain activity are recommended and epidemiological control measures should be established.

Bronchiectasis: a retrospective study of clinical and aetiological investigation in a general respiratory department.

BACKGROUND: Bronchiectasis can result from many diseases, which makes the aetiological investigation a complex process demanding special resources and experience. The aetiological diagnosis has been proven to be useful for the therapeutic approach. OBJECTIVE: Evaluate how accurately and extensive the clinical and aetiological research was for adult bronchiectasis patients in pulmonology outpatient service which were not following a pre-existing protocol. METHODS: We retrospectively reviewed the records of 202 adult patients with bronchiectasis, including the examinations performed to explain the aetiology. RESULTS: The mean age of the patients was 54 ± 15 years, there was a predominance of female (63.9%) and non-smoker (70%) patients. Functional evaluation showed a mild airway obstruction. The sputum microbiological examination was available for 168 patients (43.1% had 3 or more sputum examinations during one year). Immunoglobulins and α1-antitrypsin were measured in around 50% of the patients. The sweat test and the CF genotyping test were performed in 18% and 17% of the patients, respectively. The most commonly identified cause was post-infectious (30.3%), mostly tuberculosis (27.2%). No definitive aetiological diagnosis was established in 57.4% of the patients. We achieved a lower aetiological diagnosis if we compare our series with studies in which a diagnostic algorithm was applied prospectively. CONCLUSIONS: The general characteristics of our patients were similar with other series. Detailed investigation of bronchiectasis is not a standard practice in our outpatient service. These results suggest that the use of a predefined protocol, based on current guidelines, could improve the assessment of these patients and facilitate the achievement of a definitive aetiology.

Diagnostic value of bronchoalveolar lavage in suspected pulmonary tuberculosis.

Of 222 patients suspected of having pulmonary tuberculosis (PT), studied during a one-year period, we performed fiberoptic bronchoscopy together with bronchoalveolar lavage (BAL), bronchial washing and postbronchoscopy sputum smears and Löwenstein cultures in 20 patients. Bronchoalveolar lavage proved to be the most effective method leading to diagnosis in 17 of 20 cases. Diagnosis was obtained in 11 of 20 cases using bronchial washing and postbronchoscopy sputum. The results of this study suggest that bronchoscopy may be required in selected cases for the diagnosis of PT. However, it should be accompanied by BAL, bronchial washings and postbronchoscopy sputum smears. Indications for bronchoscopy as a diagnostic tool for PT may include: (a) patients suspected of having PT with negative smears and in whom treatment must be started due to clinical status; (b) suspicion of associated neoplasia; (c) selected patients with negative Löwenstein cultures; (d) lack of material being obtained by simpler methods.

Specific antibody response against the 23-valent pneumococcal vaccine in patients with alpha(1)-antitrypsin deficiency with and without bronchiectasis.

OBJECTIVE: To assess the specific antibody response against polyvalent pneumococcal vaccine in patients with alpha(1)-antitrypsin deficiency (AATD) and respiratory infections. DESIGN AND PARTICIPANTS: We investigated specific IgG, IgG1, and IgG2 antibody responses against the 23-valent antipneumococcal vaccine in 18 patients with AATD phenotype PiZZ, 9 of whom had bronchiectasis and 4 a history of recurrent pneumonia, and compared them with a control group of 40 healthy volunteers. INTERVENTIONS: Blood samples were drawn just prior to and 3 weeks after immunization. MEASUREMENTS AND RESULTS: Quantification of specific IgG and its subclasses was performed by an enzyme-linked immunosorbent assay. For patients with AATD, mean increases in specific antipneumococcal titers were 4.7-fold (25 to 75% quartiles, 2.5- to 6.8-fold) for total IgG, 3.2-fold (1.2- to 4.9-fold) for IgG1, and 2.1-fold (1.8- to 3.7-fold) for IgG2. For the control group, the values were 3.3-fold (1.8- to 5.8-fold) for total IgG, 2. 5-fold (1.9- to 3.4-fold) for IgG1, and 3.1-fold (1.9- to 4.5-fold) for IgG2; differences were not significant. Patients with bronchiectasis showed a tendency toward higher levels of IgG subclasses than both control subjects and patients without bronchiectasis; however, there was a tendency toward lower postvaccination serum levels of specific antipneumococcal IgG, IgG1, and IgG2 in patients with bronchiectasis compared with patients without bronchiectasis, but this trend did not reach statistical significance. Three of the four patients with recurrent pneumonia did not show an appropriate IgG2 response. CONCLUSIONS: These results suggest that, as a group, patients with AATD have a preserved antibody response against pneumococcal polysaccharides. Patients with bronchiectasis show a tendency toward a decreased antibody response, even with increased serum levels of most Ig types. Individuals with an impaired IgG2 response seem to be at increased risk of recurrent pneumonia. Considering the pernicious effect of pulmonary infections on these patients and the preserved antibody response in a majority of them, pneumococcal vaccination should be recommended to patients with AATD.

Gastrointestinal, liver, and pancreatic involvement in adult patients with cystic fibrosis.

BACKGROUND: The clinical prevalence of cystic fibrosis (CF) in adults continues to rise, with a consequent impact on adult gastroenterology practice. AIM: To characterize the gastrointestinal manifestations of CF in adult patients. PATIENTS AND METHODS: The clinical records of 89 adult CF patients treated at our institution from 1992 to 1999 were reviewed. Patients were distributed into two groups: group A (39 patients), which consisted of patients who were diagnosed with CF at when they were younger than 14 years old and who survived into adulthood; and group B (50 patients), who were diagnosed with CF at the age of 14 years or older. Data on CF genetic mutations, nutritional state, evidence of pulmonary, gastrointestinal, liver, or pancreatic involvement were collected for each patient. RESULTS: The most prevalent genetic mutation in our series was deltaF508, present in 50 patients (56.2%), 29 of whom belonged to group A and 21 who belonged to group B. In group A, the deltaF508 mutation was associated with exocrine pancreatic insufficiency (PI) in 26 of 29 patients (89.6%), whereas in group B it was associated with PI in only four patients (19%). Overall, PI was present in 33 of 39 patients (84.6%) in group A and in eight of 50 patients (16%) in group B. Four patients in group B had experienced previous episodes of acute pancreatitis; two of them had associated PI. Of the 89 patients, 12 (10 in group A) were malnourished. Malnutrition was invariably associated with PI. Hepatic and biliary tree abnormalities were particularly prevalent in patients in group A and was usually associated with PI. Intestinal manifestations were uncommon. CONCLUSIONS: Diagnosis of CF before the age of 14 years is associated with greater gastrointestinal compromise than diagnosis at an older age, particularly with regard to PI. CF carriers of the deltaF508 mutation have an increased risk of developing gastrointestinal manifestations.

Time of exposure as a prognostic factor in avian hypersensitivity pneumonitis.

Spirometric values were subsequently evaluated in 22 patients suffering from hypersensitivity pneumonitis caused by avian problems. First spirometric values were abnormal in 18/22 (82%) of patients. A restrictive pattern was observed in 16/22 (72%) of patients and an obstructive pattern in 6/22 (27%). The TLCO was reduced in all cases (12/12). Improvement or normalization of the respiratory function occurred 3.4 +/- 2.4 months after the avian contact had ceased. At the end of the follow-up, parameters were normal in 13/22 (59%) of patients. The restrictive pattern remained unchanged in 7/22 (32%), and the obstructive pattern persisted in 4/22 (18%) of the patients. The TLCO was normal in 6/12 (50%) of patients. Neither age nor treatment with corticosteroids (13 patients) had a significant influence upon the evolution of the lung function. However, total recovery or significant improvement was observed in 12/12 (100%) of patients who had been in contact with birds less than 2 years, in contrast to 6/10 (60%) of patients with more than 2 years of contact (P = 0.002).

[Theophyllines of 12- and 24-hour sustained-release. Comparative study]. / Teofilinas de liberación sostenida de 12 y 24 horas. Estudio comparativo.

To compare 24-h and 12-h delayed-release theophylline in asthmatic patients, in terms of clinical stability and respiratory function, side effects and required dose, clinical tolerance and plasma concentrations. Patients with bronchial asthma in stable phase taking theophylline every 12 h were selected. Each patient received 12-h (treatment A) and 24-h (treatment B) theophylline formulas in a prospective, cross-over study with paired data for periods of 15 days. We evaluated theophylline doses, blood levels, clinical course, lung function and side effects. Twenty patients were enrolled. No significant differences between the two treatments were observed in mean dose of theophylline per kg body weight required to obtain therapeutic plasma concentrations (treatment A: 9.36 +/- 1.88 mg/kg/day; treatment B: 9.6 +/- 1.7 mg/kg/day). Mean blood level just before administration of a the next dose was lower with the 24-h formula, but still within therapeutic margins (treatment A: 7.31 +/- 2.27 micrograms/ml; treatment B: 10.66 +/- 2.86 micrograms/ml; p = 0.002). There were no differences in side effects after the adjustment period or in FEV1 after each treatment period. Peak expiratory flow remained stable during the study. The 24-h delayed release theophylline formula was similar to the 12-h formula in dose required by asthmatic patients and in therapeutic plasma concentrations throughout the day.

[The use of fibrinogen-thrombin via endoscope in the treatment of massive hemoptysis]. / Utilización de fibrinógeno-trombina por vía endoscópica en el tratamiento de la hemoptisis masiva.

We assessed the efficacy of fibrinogen-thrombin instillation through the fiberoptic bronchoscope to treat massive hemoptysis in patients to whom embolization of bronchial arteries was not available, was contraindicated or had failed. The fibrinogen-thrombin solution used was Tissucol, which in addition to 2% fibrinogen and 4 U/ml of thrombin, also contained factor XIII an aprotinin. The fibrinogen-thrombin solution was instilled with the aid of the Duplojec system and a 70 cm x 2 mm 4-way catheter. In 53 of the 628 fiberoptic bronchoscopies performed during the study, the indication was hemoptysis > or = 150 ml/12 h. Of these, bronchoscopic instillation of fibrinogen-thrombin was indicated in 5 cases because bronchial artery embolization was impossible. The point of bleeding was located by bronchoscopy in all cases and fibrinogen-thrombin instillation controlled hemoptysis immediately and throughout the follow-up period, which ranged 4 to 10 months. Morning expectoration of blood (< 10 ml) was observed in only 1 patient in the 3 days after treatment. The mean time taken for bronchoscopic exploration was 3 minutes (range, 2-7). In all cases fiberoptic bronchoscopy was performed without complications that might have required the procedure to be suspended. We conclude that the local use of fibrinogen-thrombin or fibrin glue instilled through the fiberoptic bronchoscope to the point of bleeding is a simple, fast and cheap way to control massive hemoptysis on a short and long-term basis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of replacement therapy in emphysema caused by alpha 1-antitrypsin deficiency]. / Evaluación del tratamiento sustitutivo del enfisema por déficit de alfa-1-antitripsina.

Assessment of alpha 1-antitrypsin replacement therapy (AAT) for emphysema. Patient characteristics were analyzed along with the possible side effects of the treatment and its efficacy in maintaining appropriate AAT blood levels. Lung function changes were also studied. The treatment protocol began with 4 weekly intravenous doses of 60 mg/kg AAT (Prolastin) and continued with monthly doses of 240 mg/kg. AAT serum levels were measured before each dose. Every 6 months pulmonary function tests (spirometry, plethysmography and CO transfer) were performed. Thirteen patients (mean age 46 yr) have been studied since 1988. Mean initial FEV1 was 0.79 l. Over 250 doses have been infused with no significant side effects reported. AAT levels before treatment in 3 patients were lower than that considered protective (50 mg/dl). Function tests results indicated stabilization of spirometric values in most cases. Diagnosis of AAT deficiency is delayed considerably, meaning that significant functional deterioration takes place before replacement therapy begins. No side effects of treatment have been observed. Until an appropriate interval between doses has been established, each patient's AAT levels must be monitored.

[A contagiousness study in 3071 familial contacts of tuberculosis patients]. / Estudio del contagio en 3.071 contactos familiares de enfermos con tuberculosis.

BACKGROUND: The study of contacts of patients with tuberculosis is an important preventive measure which helps to identify the risk factors for contagion, to detect new cases of the disease early and to break the epidemiological chain of transmission. MATERIAL AND METHOD: Three thousand and seventy-one contacts of 635 patients with tuberculosis were studied in our department over a period of 6 years. With the aid of uni- and multivariate analyses we established the importance of different factors in the appearance of tuberculous disease and infection in contacts. RESULTS: There were 1,341 tuberculin positive contacts (44%). The proportion increased in relation to the degree of the relationship and the bacillary density of the index case. A hundred and seventy-six new cases of tuberculosis were diagnosed among the contacts (5.7%). To study the risk factors for contagion, we analyzed the characteristics of 322 patients with positive sputum smears and their 1,623 contacts; 124 new cases were diagnosed among them (124/176; 70%). The most important factors for contagion in the multivariate analysis were the closer relationship (odds ratio [OR] = 8.32; confidence interval [Cl] 95% = 3.9-17.6), greater TST reaction of contacts (OR = 4.43; Cl 95% = 2.5-7.7), presence of more than 10 bacilli per microscopic field in the sputum samples of the index case (OR = 1.97; Cl 95% = 1.1-3.3), male contacts (OR = 1.86; Cl 95% = 1.2-2.7) and those younger than 15 years (OR = 1.58; Cl 95% = 1.01-2.45). Conversely, the sex of the index case and the history of previous tuberculosis in contacts did not influence the contagion. CONCLUSIONS: The study of contacts offers a high yield in the diagnosis of new tuberculosis cases, because the incidence of the disease is much higher than that of the general population. Moreover, it allows the detection of newly infected subjects in whom the application of chemoprophylaxis prevents the development of the disease, and thus the epidemiologic chain of transmission is broken.

[IgG subclasses in patients with symptomatic IgA deficiency]. / Estudio de las subclases de la IgG en pacientes con déficit de IgA sintomáticos.

BACKGROUND: Patients with IgA deficiency may be asymptomatic or may present recurrent infections mainly respiratory. A possible explanation for this variety of symptoms may be the association with a deficiency of IgG subclasses. METHODS: Twenty-five patients with a symptomatic IgA deficiency with a mean age of 18 +/- 12 years were studied. The quantification of the IgG subclasses was performed by ELISA test with antisubclass specific monoclonal murine antibodies. Serum from 100 healthy adults was collected to determine normal values of the IgG subclasses. RESULTS: Twenty-five (48%) had a deficiency of associated IgG subclasses (6 IgG2 deficiency, 1 IgG3, 3 IgG4 and 2 combined deficiency). The patient with a deficiency of associated IgG subclasses had more recurrent respiratory infections (chi 2, p < 0.03) and pneumonias (chi 2, p < 0.04). This group also had a greater FEV1 alteration (Student-t test, p < 0.04). CONCLUSIONS: Patients with symptomatic IgA deficiency frequently present IgG subclass deficiency and are more likely to have recurrent respiratory infections and greater changes in pulmonary function.

[Familial microepidemics of tuberculosis]. / Microepidemia familiar de tuberculosis.

We report a microepidemic of tuberculosis (TBC) in a family of 12 members, 4 of which were parenteral drug abusers and 3 had anti-human immunodeficiency virus (HIV) antibodies. Four new cases were simultaneously diagnosed in the investigation of the contacts of a patient with extrapulmonary tuberculosis and acquired immunodeficiency syndrome. We review the requirements for the development of these epidemic outbreaks, both in noninfected communities and in the family contacts, where positive anti-HIV antibodies may increase the risk. We emphasize the importance of a systematic study of contacts in these families and the indication of chemoprophylaxis in all those sharing the same household, without age limit.

[Normal values of the immunoglobulin G subclasses in an adult population. Importance in a study of their deficiency]. / Valores normales de las subclases de la inmunoglobulina G en una población de adultos. Su importancia en el estudio de los déficit de las mismas.

BACKGROUND: Quantification of the IgG subclasses (IgGS) requires highly sensitive and specific techniques since their molecular structure is more than 95% homologous. At present, ELISA and RIA are the most appropriate techniques; although the variability of these techniques and the possible ethnic differences in serum levels of IgGS oblige each laboratory to establish its own reference values in a normal population, a condition necessary for defining IgGS deficits. METHODS: In the present study the normal serum values of IgGS in 100 healthy individuals were established. Serum quantification of the IgGS was performed by optimization of the indirect ELISA technique using AcMo and OMS reference standards H00-03 for the 4 subclasses, calibrated vs the OMS WHO 67/97 pattern. RESULTS: Normal values observed for IgG1 were 2.61-10.81 g/l; IgG2, 1.12-4.08 g/l; IgG3, 0.22-2.88 g/l; and IgG4, 0.05-1.56 g/l obtained as of the mean +/- 2 SD for IgG1 and as of the extent of the values of the remaining 3 subclasses by following a non-normal distribution. The sensitivity of the technique was 0.05 g/l with mean intra and inter analysis coefficients of 3.5% and 10.7% respectively. The correlation between total IgG and the sum of the 4 subclasses showed a r = 0.894 (p less than 0.01). CONCLUSIONS: The ELISA technique using AcMo and OMS reference standards is an adequate method for the quantification of the IgG subclasses. However, given the variability of this technique and in order to avoid error, strict working conditions, such as the use of control sera at 2 concentration levels, should be observed for the 4 IgGS in each of the analytic series and each series should also be duplicated.

[The use of human gamma globulin in the treatment of common variable immunodeficiency]. / Utilización de gammaglobulina humana en el tratamiento de la inmunodeficiencia común variable.

BACKGROUND: The indication for treatment with human gammaglobulin in patients with primary hypogammaglobulinemia is well established. Nonetheless, there are no uniform criteria with regard to dose, periodicity and route of administration. METHODS: Twenty-seven patients with common variable immunodeficiency (CVI) who received i.m. or i.v. treatment with gammaglobulin were studied, evaluating the secondary effects, stable levels of IgG achieved, control of symptomatology, clinical evolution and the need for adjuvant therapies. RESULTS: Intravenous administration was more effective than intramuscular administration to achieve higher total IgG serum levels (5.2 +/- 1.2 vs 3.5 +/- 1.6 g/l; p = 0.07) in a shorter period of time (2.1 +/- 1.6 months vs 6.3 +/- 2.8 months; p < 0.01) and with new few secondary effects. The dose and periodicity of the treatment was individualized in each patient on the basis of the needs of consumption and the speed of metabolism of the gammaglobulin, with patients with chronic bronchial suppuration and diarrhea being those requiring the greatest doses (p < 0.0001) and a short interdosis time interval (19.2 +/- 3.1 vs 23.6 +/- 3.6 days; p = 0.01). Treatment with human gammaglobulin allowed the control of recurrent bacterial infection; however, adjuvant treatment with respiratory physical measures and antibiotics were required in patients with chronic bronchial suppuration to avoid progressive alteration of respiratory function. CONCLUSIONS: The administration of human gammaglobulin at adequate doses and frequency is effective to control infection, avoid the development of chronic bronchial disease, alteration of pulmonary function and the appearance of other complications. Intravenous route is safer and produces fewer secondary effects than intramuscular administration with the doses and period of the treatment requiring individualization for each patient.