lactoferrin and Asthma

Agennix is developing recombinant human (rh) lactoferrin, a glycoprotein with antibiotic, anti-inflammatory and immunomodulatory activity, for the potential treatment of cancers, asthma and chronic wounds. rh Lactoferrin is currently undergoing phase II clinical trials.

Topics: Aspergillus; Asthma; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Humans; Lactoferrin; Neoplasms; Recombinant Proteins; Wound Healing; Wounds and Injuries

Topics: Anaphylaxis; Anti-Glomerular Basement Membrane Disease; Antigen-Antibody Complex; Asthma; Complement System Proteins; Cytotoxicity, Immunologic; Humans; Immunoglobulins; Interferons; Lactoferrin; Leukocytes; Lung; Macrophages; Muramidase; Phagocytosis; Reagins; Respiratory Hypersensitivity; Rhinitis, Allergic, Seasonal; Sarcoidosis; Tuberculosis, Pulmonary

The object of this investigation was to study the long-term effects of antiasthma treatment on blood markers of inflammation and lung function in adult asthmatic subjects. For this purpose 85 allergic and nonallergic asthmatic subjects were randomized into three groups, which were given high-dose (1,600 micrograms/d) inhaled budesonide, low-dose (400 micrograms/d) inhaled budesonide, and oral theophylline (600 mg/d), respectively, and were followed for 11 mo with testing of lung function and blood sampling for the assay in serum of eosinophil cationic protein (ECP), eosinophil protein x/eosinophil derived neurotoxin (EPX/EDN) as eosinophil markers, and myeloperoxidase (MPO) and lactoferrin (LF) as neutrophil markers. Lung functions (FEV1% predicted, and histamine PC20) and the eosinophil markers ECP and EPX/EDN were improved and reduced, respectively, by budesonide in a dose-dependent and temporally parallel fashion. Theophylline did not alter lung functions but reduced ECP and EPX/EDN after prolonged treatment. The treatment efficacy of budesonide was attributed solely to an effect on nonsmoking asthmatic subjects, since neither lung functions nor eosinophil markers changed in smokers even with high-dose budesonide. MPO but not LF was reduced after several months of treatment in all three groups, but only in nonsmokers. We conclude that ECP and EPX/EDN may be used to monitor antiinflammatory treatment in asthmatic patients, and that smoking asthmatic subjects are resistant to inhaled corticosteroids.

Topics: Adult; Aerosols; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Biomarkers; Blood Proteins; Bronchodilator Agents; Budesonide; Dose-Response Relationship, Drug; Eosinophil Granule Proteins; Eosinophil-Derived Neurotoxin; Eosinophils; Female; Follow-Up Studies; Forced Expiratory Volume; Humans; Inflammation Mediators; Lactoferrin; Lung; Male; Middle Aged; Neurotoxins; Neutrophils; Peroxidase; Pregnenediones; Ribonuclease, Pancreatic; Ribonucleases; Smoking; Theophylline

Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, and antitumoral activities. LF has been shown to function in immunoregulatory activities in ovalbumin (OVA)-induced delayed type hypersensitivity (DTH) in mice. Hence, the purpose of this study was to investigate the roles of LF in AHR and the functions of dendritic cells (DCs) and Th2-related responses in asthma. Twenty 8-week-old male BALB/c mice were divided into normal control (NC), ovalbumin (OVA)-sensitized, and OVA-sensitized with low dose of LF (100 mg/kg) or high dose of LF (300 mg/kg) treatment groups. The mice were challenged by intranasal instillation with 5% OVA on the 21st to 27th day after the start of the sensitization period. The AHR, cytokines in bronchoalveolar lavage fluid, and pulmonary histology of each mouse were measured. Serum OVA-specific IgE and IgG1 and OVA-specific splenocyte responses were further detected. The results showed that LF exhibited protective effects in ameliorating AHR, as well as lung inflammation and damage, in reducing the expression of Th2 cytokines and the secretion of allergen-specific antibodies, in influencing the functions of DCs, and in decreasing the level of Th2 immune responses in a BALB/c mouse model of OVA-induced allergic asthma. Importantly, we demonstrated that LF has practical application in reducing DC-induced Th2 cell responses in asthma. In conclusion, LF exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma. These results suggest that LF may act as a supplement to prevent asthma-induced lung injury and provide an additional agent for reducing asthma severity.

Topics: Animals; Asthma; Cytokines; Dendritic Cells; Lactoferrin; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells

Fluticasone propionate uptake in the presence of a proprietary cell-penetrating peptide (human stimulus factor, [HSF]) based on the N-terminal domain of lactoferrin was studied, alone and in combination with salmeterol, using an air interface Calu-3 epithelial model. The HSF enhanced uptake and transport of fluticasone propionate across the epithelial barrier when alone and in presence of salmeterol. This was attributed to transcellular-mediated uptake. This HSF is a promising peptide for delivery of therapeutics where enhanced epithelial penetrating is required.

Topics: Administration, Inhalation; Asthma; Bronchodilator Agents; Cell Line, Tumor; Cell Membrane; Drug Carriers; Drug Combinations; Fluticasone; Humans; Lactoferrin; Peptides; Permeability; Protein Domains; Pulmonary Disease, Chronic Obstructive; Respiratory Mucosa; Salmeterol Xinafoate

Topics: Adult; Asthma; Bifidobacterium; Breast Feeding; Child, Preschool; Diabetes Mellitus; Dietary Supplements; Enterocolitis, Necrotizing; Female; Gastrointestinal Microbiome; Health; Humans; Infant; Infant, Newborn; Lactobacillus; Lactoferrin; Microbiota; Milk, Human; Neonatology; Oligosaccharides; Parturition; Pregnancy; Probiotics; Proteobacteria

Lactoferrin in commercial supplements is known to exert anti-viral and anti-allergic effects. However, this is the first study to evaluate the induction of allergic airway inflammation in NC/Nga mice. Human lactoferrin was administered intraperitoneally with aluminum oxide for sensitization. Five days later, lactoferrin was inoculated intranasally for 5 days, and then on the 12th day, the single inoculation of lactoferrin intranasally was performed as a challenge. On the 13th day, airway hypersensitivity was assessed (AHR), a bronchoalveolar fluid (BALF) cell analysis was conducted, serum IgE and serum lactoferrin-specific IgG and IgE levels as well as the mRNA expression levels of cytokines and chemokines in the lung were measured, and a histopathological analysis of the lung was performed. Human lactoferrin increased AHR, the number of eosinophils in BALF, serum lactoferrin-specific IgG levels, and the mRNA levels of IL-13, eotaxin 1, and eotaxin 2. Moreover, the accumulation of inflammatory cells around the bronchus and the immunohistochemical localization of arginase I and human lactoferrin were detected. Collectively, these results indicate that human lactoferrin induced allergic airway inflammation in mice. Therefore, the commercial use of human lactoferrin in supplements warrants more intensive study.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Chemokine CCL11; Chemokine CCL24; Cytokines; Immunoglobulin E; Immunoglobulin G; Lactoferrin; Lung; Male; Mice; RNA, Messenger

Despite the evidence that Lactoferrin (Lf) is involved in allergic asthma processes, it is unknown whether neutrophils can be one of the main cellular sources of this key inflammatory mediator directly in response of an IgE mediated stimulus. The present study was undertaken to analyze this question.. Neutrophils from healthy subjects (n = 34) and neutrophils from allergic asthmatic patients (n = 102) were challenged in vitro with specific allergens to which the patients were sensitized, PAF, or agonist mAbs against IgE-receptors, and the levels of Lf were measured in the culture supernatant. The levels of serum IgE together with the severity of symptoms were also analyzed.. Lf was released into the culture supernatant of neutrophils from allergic asthmatic patients in response to allergens and PAF. This response was highly allergen-specific, and did not happen in neutrophils from healthy donors. Allergen effect was mimicked by Abs against FcεRI and galectin-3 but not by FcεRII. The levels of released Lf correlated well with the levels of serum specific IgE and severity of asthma symptoms. These observations represent a novel view of neutrophils as an important source of Lf in allergic asthma. Importantly, the levels of released Lf by neutrophils could therefore be used to evaluate disease severity in allergic asthmatic patients.

Topics: Adolescent; Adult; Allergens; Asthma; Case-Control Studies; Female; Galectin 3; Humans; Immunoglobulin E; Lactoferrin; Male; Middle Aged; Neutrophils; Receptors, IgE; Young Adult

Topics: Asthma; Case-Control Studies; Cytokines; Disease Progression; Eosinophils; GPI-Linked Proteins; Humans; Immunohistochemistry; Inflammation; Interleukin-13; Lactoferrin; Lectins; Mucus; Up-Regulation

The authors previously showed that pollen grain-, pollen grain extract-. and subpollen particle-induced allergic inflammation in lungs and eyes is robustly augmented by their intrinsic NAD(P)H oxidase activity. Here they sought to determine whether lactoferrin (LF), an iron-binding protein and immune modulator, decreases allergic inflammation induced by ragweed (Ambrosia artemisiifolia) pollen grain extract (RWE).. The impact of LF on NAD(P)H oxidase in pollen grains and reactive oxygen species (ROS) levels in vitro and in the lungs of experimental animals was assessed by use of redox-sensitive probes and specific inhibitors. The influence of LF on RWE-induced allergic inflammation was determined in a mouse experimental model of asthma.. The data show that the intrinsic NAD(P)H oxidase of pollen grains generates superoxide anion (O2-) and that LF does not alter its enzymatic activity, as shown by nitroblue tetrazolium and cytochrome c assays. On the other hand, LF significantly decreased H(2)- O(2)- and lipid peroxide (4-hydroxynoneal and malondialdehyde) levels in airway lining fluids and lung epithelium after intranasal challenge of naive or sensitized mice with RWE. Furthermore, a single dose of LF prevented/decreased the abundance of the RWE-induced robust accumulation of inflammatory and mucin-producing cells in airways and subepithelial compartments and decreased airway hyperreactivity.. These data suggest that the reduced conversion of NAD(P)H oxidase-generated O(2)- into H(2)- O(2)- and/or OH, which in turn synergistically enhanced pollen antigen-induced airway inflammation, is due to the iron-binding capacity of LF. These results support the utility of LF in human allergic inflammatory disorders.

Topics: Allergens; Analysis of Variance; Animals; Antigens, Plant; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Cells, Cultured; Disease Models, Animal; Female; Lactoferrin; Mice; Mice, Inbred BALB C; Oxidative Stress; Plant Proteins; Pollen; Superoxides

Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and in contact with mucosal surfaces generate superoxide anion (O2*-). In the presence of iron, O2*- may be converted to more reactive oxygen radicals, such as to H2O2 and/or *OH, which may augment antigen-induced airway inflammation. The aim of the study was to examine the impact of lactoferrin (LF), an iron-binding protein, on ragweed (Ambrosia artemisiifolia) pollen extract (RWE)-induced cellular oxidative stress levels in cultured bronchial epithelial cells and accumulation of inflammatory and mucin-producing cells in airways in a mouse model of allergic airway inflammation. Results show that LF lowered RWE-induced increase in cellular reactive oxygen species (ROS) levels in bronchial epithelial cells. Most importantly, LF significantly decreased accumulation of eosinophils into airways and subepithelium of intranasally challenged, sensitized mice. LF also prevented development of mucin-producing cells. Amb a 1, the major allergenic ragweed pollen antigen lacking NADPH oxidase activity, induced low-grade airway inflammation. When administered along with glucose oxidase (G-ox), a superoxide-generating enzyme, Amb a 1 induced robust airway inflammation, which was significantly lowered by LF. Surprisingly, LF decreased also inflammation caused by Amb a 1 alone. Iron-saturated hololactoferrin had only a marginal effect on RWE-induced cellular ROS levels and RWE- or Amb a 1 plus G-ox-induced inflammation. We postulate that free iron in the airways chemically reduces O2*- to more reactive species which augment antigen-induced inflammation in a mouse model of asthma. Our results suggest the utility of LF in human allergic inflammatory disorders.

Topics: Allergens; Ambrosia; Animals; Antigens, Plant; Asthma; Bronchi; Bronchoalveolar Lavage Fluid; Cells, Cultured; Disease Models, Animal; Female; Lactoferrin; Mice; Mice, Inbred BALB C; Oxidative Stress; Plant Proteins; Pollen; Reactive Oxygen Species

The objective of this forensic autopsy study was to determine the immunohistochemical expression pattern of lactoferrin (LF) in pulmonary tissue sections deriving from fatal slow-onset asthma (time interval between onset of asthma attack and death >2.5 h) and fatal sudden-onset asthma (cases in which death occurred within 1 h of the onset of an asphyxic asthma attack) relative to controls (sudden death due to diseases other than respiratory disorders). LF was applied to paraffin sections using a standard peroxidase-labelled streptavidin-biotin technique. LF immunoreactivity was graded semi-quantitatively in relation to different histoanatomic distribution sites of LF on a five category ordinal scale (maximum score of 15). We found a statistically significant difference between an enhanced expression of LF in both asthma groups relative to the controls (P<0.004 and P<0.001, respectively). When comparing both asthma groups, there was a statistically significant difference in LF immunoreactivity between the slow-onset and sudden-onset asthma group (P<0.001). Since LF immunoreactivity was far less intense in the sudden-onset asthma group (mean expression +/-SD: 7.3+/-1.3) than in the slow-onset asthma group (12.5+/-1), and an absent or weak LF expression pattern was observed in the control group (1.4+/-1.3), we assume that our results permit the following cautious estimations: (1) pulmonary LF expression is enhanced in asthma attacks with fatal outcome relative to controls and (2) a different expression pattern of LF can be observed in fatal sudden-onset asthma compared to slow-onset asthma in so far as the pulmonary expression of LF seems to be positively correlated with the preceding period of time between the asphyxic asthma attack and death. Further clinicopathologic studies including in-patient asthma fatalities with a well-known medical history are required to scrutinize if the pulmonary expression of LF is in fact positively associated with the time span of the asthma attack, thus possibly providing further therapeutic opportunities to intervene in severe asphyxic asthma.

Topics: Acute Disease; Adolescent; Adult; Aged; Asthma; Cause of Death; Child; Chronic Disease; Death, Sudden; Female; Forensic Medicine; Humans; Lactoferrin; Lung; Male; Middle Aged

The number of decayed, missed and filled permanent teeth (DMFT), the degree of periodontal inflammation (Periodontal Status Index, PSI), stimulated salivary flow rate and the concentrations of total protein, lactoferrin, lysozyme, myeloperoxidase, salivary peroxidase, calcium, potassium, sodium and thiocyanate in whole saliva of 26 adult asthma patients were compared with those of 33 non-asthmatic controls. The saliva was also analysed for mutans streptococci, lactobacilli, total anaerobic flora and Candida spp. The mean PSI (p < 0.05; 95% confidence interval for the difference between means (95% CI) 2.47-25.30) was higher and the mean stimulated salivary flow rate (p < or = 0.05; 95% CI 0.57-0.55) was lower in the asthmatic group than in the control group. No differences were found between the groups in non-immune defense factors, except for myeloperoxidase. The myeloperoxidase concentrations were higher in asthmatics than in non-asthmatics (p < 0.05; 95% CI 4.4-134.0 ng/ml). No differences in microbial counts were found. It was concluded that stimulated salivary flow rates decrease while myeloperoxidase concentrations increase in adult asthmatic patients compared with non-asthmatic adults. The higher concentrations of myeloperoxidase are explained by a higher PSI in asthmatics.

Topics: Adult; Asthma; Bacteria, Anaerobic; Calcium; Candida; Colony Count, Microbial; Confidence Intervals; DMF Index; Female; Humans; Lactobacillus; Lactoferrin; Male; Middle Aged; Muramidase; Periodontal Index; Periodontitis; Peroxidase; Peroxidases; Potassium; Saliva; Salivary Proteins and Peptides; Secretory Rate; Sodium; Streptococcus mutans; Thiocyanates

Tryptase, a serine protease released exclusively from activated mast cells, has been implicated as a potential causative agent in asthma. Enzymatically active tryptase is comprised of four subunits, and heparin stabilizes the associated tetramer. Lactoferrin, a cationic protein released from activated neutrophils, binds tightly to heparin, therefore we investigated lactoferrin as an inhibitor of tryptase and found that it is both a potent (Ki' is 24 nM) and selective inhibitor. Size exclusion chromatography studies revealed that lactoferrin disrupted the quaternary structure of active tryptase. Lactoferrin was tested in an allergic sheep model of asthma; aerosolized lactoferrin (10 mg in 3 ml phosphate-buffered saline, 0.5 h before as well as 4 and 24 h after inhalation challenge by Ascaris suum) abolished both late-phase bronchoconstriction (no significant increase in specific lung resistance 4 to 8 h following provocation, p < 0.05 versus vehicle treatment) and airway hyperresponsiveness (no detectable increase in airway sensitivity to carbachol challenge 24 h after antigen challenge, p < 0.05 versus vehicle). These data suggest tryptase involvement in both late-phase bronchoconstriction and airway hyperreactivity and furthermore suggest that a physiological function of neutrophil lactoferrin is the inhibition of tryptase released from mast cells.

Topics: Airway Resistance; Animals; Asthma; Blotting, Western; Bronchial Hyperreactivity; Bronchoconstriction; Chromatography, Gel; Chymases; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Lactoferrin; Rats; Respiratory Hypersensitivity; Serine Endopeptidases; Serine Proteinase Inhibitors; Sheep; Time Factors; Tryptases

We have investigated whether IL-8 is present in airway secretions from patients with asthma and chronic obstructive pulmonary disease (COPD) to obtain information on its possible role in airway inflammation in obstructive airways disease. In the bronchoalveolar lavage fluid (BALF) from 11 clinically stable patients with asthma the levels of IL-8 were increased compared to 10 healthy subjects (median: controls 21.5 pg/ml, asthma 244 pg/ml: p < 0.005). In the patients with asthma the levels of IL-8 correlated with the percentage neutrophils in the BALF (r = 0.81; p < 0.001) and with a parameter of the permeability of the respiratory membrane, the quotient (alpha 2-macroglobulin in BALF)/(alpha 2-macroglobulin in serum) (r = 0.66; p < 0.025). In the sputum sol phase of 9 patients with symptomatic asthma the levels of IL-8 were lower than in 9 patients with COPD (asthma: 6.4 ng/ml; COPD: 16.3 ng/ml; p < 0.02) and significantly correlated with those of neutrophilic myeloperoxidase (MPO; r = 0.85; p < 0.005). The increased levels of IL-8 in the airway secretions from both patients with asthma and COPD may be markers of an ongoing inflammatory process, which is more pronounced in patients with COPD. In patients with asthma the strong correlation between the levels of IL-8 and the percentage neutrophils and/or the levels of MPO points to a role of IL-8 in the recruitment and activation of neutrophils in the airway lumen.

Topics: Adolescent; Adult; Aged; Asthma; Blood Proteins; Bronchoalveolar Lavage Fluid; Eosinophil Granule Proteins; Humans; Immunoglobulin A, Secretory; Inflammation Mediators; Interleukin-8; Lactoferrin; Lung Diseases, Obstructive; Middle Aged; Neutrophil Activation; Neutrophils; Permeability; Peroxidase; Ribonucleases; Sputum

To determine whether markers of mucus secretion can be quantified in airway lining fluid from asthmatic and from healthy subjects, we measured levels of a mucin-like glycoprotein (MLG) and lactoferrin in sputum induced by inhalation of hypertonic (3%) saline in 18 asthmatic and in 10 healthy subjects. Because DNA, like mucin, contributes to the viscosity of airway secretions, we also measured DNA levels in the induced sputum samples. To control for the presence of saliva in sputum, we also analyzed saliva samples from all subjects. The entire sputum sample and the saliva sample were reduced using dithiotreitol, and biochemical analysis was performed on supernatants obtained after centrifugation. We found that induced sputum from asthmatic subjects had higher levels of MLG [2,574.4 +/- 907.8 (mean +/- SEM) versus 562.2 +/- 90.5 micrograms/ml, p < 0.007] and DNA (7.1 +/- 1.6 versus 3.6 +/- 0.6 micrograms/ml, p < 0.05), but the difference in lactoferrin levels failed to reach statistical significance. However, in the subgroup of asthmatic subjects who gave a history of sputum production (n = 9), lactoferrin levels were higher than in the healthy control subjects (118.9 +/- 46.3 versus 35.2 +/- 6.5 micrograms/ml, p < 0.05). The very low levels of MLG, DNA, and lactoferrin measured in saliva were not significantly different in asthmatic subjects from those in healthy subjects. We conclude that measurement of markers of mucus secretion in induced sputum is feasible in asthmatic and healthy subjects, and it reveals abnormally high markers of mucus secretion in subjects with stable asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Asthma; DNA; Female; Glycoproteins; Humans; Lactoferrin; Male; Middle Aged; Mucins; Mucus; Saliva; Sodium Chloride; Sputum

Topics: Asthma; Humans; Lactoferrin; Neutrophils; Peak Expiratory Flow Rate; Peroxidase; Reference Values

We have measured lactoferrin and secretory IgA (sIgA) in the unconcentrated bronchoalveolar lavage fluid (BALF) from nonsmoking healthy volunteers (n = 10) and nonsmoking patients with stable asthma (n = 14). The median concentrations and the ranges of lactoferrin were controls, 0.13 mg/L (0.01-0.43 mg/L); asthma, 0.41 mg/L (0.07-7.51 mg/L). For sIgA the results were controls, 0.48 mg/L (0.12-1.47 mg/L); asthma, 1.29 mg/L (0.65-14.6 mg/L). The concentrations in the epithelial lining fluid (ELF) were calculated on the basis of urea in BALF and serum. SIgA and lactoferrin levels in the BALF and ELF from the patients with asthma were higher than in controls (Mann-Whitney U-test, p less than 0.03). Our results indicate that in patients with stable asthma the airway epithelial cells are activated, resulting in an enhanced secretion of lactoferrin and enhanced secretory transport of sIgA into the airway lumen.

Topics: Adolescent; Adult; Aged; Asthma; Bronchoalveolar Lavage Fluid; Female; Humans; Immunoglobulin A, Secretory; Lactoferrin; Male; Middle Aged

Possible roles of eosinophil (EO) products in modulating the release of mucus from airway explants were investigated. Cell- and membrane-free lysates from purified human EOs (1 to 20 x 10(5)) caused a dose-dependent release of respiratory glycoconjugates (RGC) from cultured feline tracheal explants. Crude extracts from isolated EO granules also stimulated RGC release, suggesting that a granular protein might be responsible. Three proteins derived from EO granules, EO-derived neurotoxin, EO cationic protein (ECP), and major basic protein (MBP) were separated by sequential sizing and affinity chromatography. ECP (0.025 to 25 micrograms/ml) caused a dose-dependent increase in RGC release from both feline and human airway explants and also stimulated the release of the serous cell-marker, lactoferrin, from human bronchial explants. EO-derived neurotoxin (0.025 to 50 micrograms/ml) failed to affect RGC release, whereas MBP (50 micrograms/ml) significantly inhibited RGC release from feline explants. Thus, ECP stimulates RGC and lactoferrin release from airway explants, whereas MBP inhibits RGC release.

Topics: Airway Obstruction; Animals; Asthma; Blood Proteins; Cats; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Eosinophil Granule Proteins; Eosinophil-Derived Neurotoxin; Eosinophils; Humans; Lactoferrin; Mucus; Neurotoxins; Organ Culture Techniques; Ribonucleases; Trachea

Topics: Adolescent; Adult; Allergens; Antigen-Antibody Complex; Asthma; Bronchial Provocation Tests; Chemotactic Factors; Female; Hot Temperature; Humans; Interleukin-8; Lactoferrin; Macrophages; Male; Monocytes; Muramidase; Neutrophils; Peak Expiratory Flow Rate

The concentrations of nine plasma proteins were determined by quantitative immunoelectrophoresis in sputum specimens from 29 patients with cystic fibrosis (CF) and from 24 patients with severe asthma and chronic bronchitis. The results suggested that the population of CF patients could be divided into two groups in spite of an absence of difference in clinical status between the groups. Average concentrations of seven plasma proteins in sputum of group I CF patients were identical with those in sputum of patients with bronchitis, but the average concentrations of six of these proteins in sputum from group II CF patients were higher than those in specimens from the bronchitic patients and were similar to corresponding concentrations in sputum from patients with asthma, all of whom were examined while in status asthmaticus. The average concentrations of 14 secretory proteins were the same in all sputum specimens whether or not they were produced by patients with cystic fibrosis, asthma or bronchitis. It was concluded that the concentrations in the bronchopulmonary secretions of proteins associated with host defence were not diminished in patients with cystic fibrosis, and failure to produce adequate concentrations of proteins with antimicrobial activity was unlikely to be responsible for the above average susceptibility to chest infection in cystic fibrosis. It is suggested that there exists a group of CF patients in whom a pulmonary allergic reaction generates an inflammatory response as severe as that characterizing status asthmaticus and that this response could be detrimental.

Topics: Adult; Aged; Albumins; Asthma; Beta-Globulins; Blood Proteins; Bronchitis; Child; Child, Preschool; Cystic Fibrosis; Female; Glycoproteins; Haptoglobins; Humans; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulin G; Lactoferrin; Male; Middle Aged; Muramidase; Sputum; Transferrin