Bronchial Adenoma.

 

                                                   Bronchial Adenoma

                                                PKGhatak, MD

Bronchial adenomas are mostly benign, but some adenomas have malignant potential and still others are low grade malignant. Bronchial adenoma arises underneath the surface layer of the mid-sized bronchus of the lower lobes of the lungs. In rare cases, adenoma originates in the peripheral bronchus. An adenoma is the second most frequent primary tumor of the lung and accounts for 5 to 15 % of all primary pulmonary tumors. Adults between 30 and 40, with or without a smoking history, develop adenoma. Incidence in females is higher. It is a slow growing tumor and can be confused with cancer of the lung because of frequent and sudden onset hemoptysis, or patients present with recurrent pneumonia of the same lobe of the lung indicating bronchial obstruction.

The tumors arise from the mucous gland or duct of the mucous gland. The tumor is small and the surface is covered with tiny blood vessels and appears red or fleshy pink when visualized during bronchoscopy, and manipulation of the tumor produces profuse bleeding. In 80% of cases, the adenomas grow with a wide base and grow towards the lumen and at times a filamentous adenoma may be found hanging in the lumen. Adenoma also grows towards the outer walls but less frequently.

Pathological types.

The adenomas are classified as Cylindroma and Carcinoid. Cylindromas are then subclassified as adrenocystic and mucoepidermoid adenomas.

Adenocytic adenoma arises from the cells of the mucus glands of the bronchus. This tumor behaves like a salivary gland tumor. Mucoepidermoids are essentially benign tumors located in the main bronchus and trachea. Structurally these tumors vary from cystic to solid and contain not only mucus producing cells but also other cell types.

Pulmonary carcinoid adenomas are no different from carcinoid tumors originating elsewhere. Carcinoids account for 80% of primary lung tumors. They arise from the Kulchitsky cells acquired during embryonic development. Bronchial carcinoids secrete serotonin and blood levels of serotonin remain high in the upper portion of the body. The high blood level of serotonin produces flushing of the face, increased tearing, redness of the chest wall, wheezing, fall of BP and tachycardia, and right ventricular valvular abnormalities. Bronchial carcinoid was discussed in greater detail in an earlier blog titled “Carcinoid and other neuroendocrine tumors”. Carcinoid tumors produce paraneoplastic syndrome by secreting various hormones - ACTH, ADH, Insulin like growth hormones. Occasionally, one carcinoid adenoma secretes multiple hormones. Carcinoid tumors are characterized by uniform closely packed clusters of polygonal to small cells.

Symptoms of bronchial adenoma.

The symptom begins with an unproductive cough, specially, when a patient is recumbent in bed or assumes a particular position. And the cough stops after changing position. Recurrent bouts of respiratory infections and pneumonia of the same lobe of the lung are the second most common presentation. Hemoptysis is common and occurs suddenly without any warning. However, hemoptysis stops spontaneously.

Chest pain, wheezing and shortness of breath are less frequent and mostly depend on the degree of bronchial obstruction.

Behavior of bronchial adenoma.

Pathological examination of bronchial carcinoids will not differentiate benign from malignant; the biological behavior of the carcinoid tumor, in time, reveals the true nature of the tumor. Only about 4 % of carcinoids are malignant and peripherally located and are more likely to be malignant.

Adenocystic adenoma behaves as a low-grade malignant tumor, spreads locally underneath the cell surface. It is difficult to know the extension of the tumor spread pre-operatively.

The centrally located mucoepidermoid is benign.

Diagnosis.

The nature of the presenting symptoms requires a prompt bronchoscopy. The tumor location, visual identification and biopsy are attempted in all cases. But since the tumors are small, tumors may not be identified in every case.

The plain chest x-ray may not show the tumor but the secondary pulmonary changes due to the bronchial obstruction – atelectasis, pneumonia, bronchiectasis and various combination of these are detected by chest x-rays. CT scans are more sensitive and detect adenoma in larger airways, but may fail to locate the really small tumors.

PET scans may miss the adenomas because of their low level of metabolic activities.

Octreotide scan for carcinoid was discussed in an earlier blog.

Biopsy.

The tissue diagnosis of cylindroma is performed by the usual staining of slides. Immunohistological staining is generally required for carcinoid tumors.

Treatment.

All bronchial tumors are removed by surgery whenever it is possible. Often, a lobe of the lung is required to be removed because of permanent pathological changes. Radiation therapy is an appropriate modality in the treatment of adenocystic tumors.

Prognosis.

The prognosis is very favorable for cylindromas. In carcinoid tumors, continued surveillance is necessary because of the unpredictable behavior of the tumor and specially the malignant carcinoid which metastasizes to the liver early.

 

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Understanding Chronic Bronchitis

 

                                        Understanding Chronic Bronchitis

                                                  PKGhatak, MD

Chronic bronchitis is hardly discussed as such nowadays, it is currently grouped together with pulmonary emphysema and is known as chronic obstructive pulmonary disease.

Shortly after the first World War, cigarette smoking became a socially cool thing and spread quickly worldwide. It did not take long before doctors in England noticed a sharp increase in chronic cough and sputum production in cigarette smokers. Doll and Hill published their landmark research paper in 1969 on the adverse effects of cigarette smoking and demonstrated the direct correlation between the number of cigarettes smoked with the incidence of lung cancer. Pathologists reported gradual changes of the respiratory epithelium of the bronchial tree to the squamous epithelium and an increase in the proliferation of mucus producing cells, Goblet cells, in smokers. Subsequently, the further transformation of squamous cells to cancer cells was demonstrated. Even then, Chronic bronchitis continued to increase and became a very common malady of that time.

It did not take long to notice that non-smokers were having chronic bronchitis too. Secondhand smoking, a new term, was coined; subsequently, coal burning smoke from factories, at home, coke or firewood burning stove fumes were linked to chronic bronchitis. It is now accepted that repeated exposures to noxious fumes, like chlorine, ammonia, etc. lead to the development of chronic bronchitis in both non-smokers and smokers.

Inhaled air travels in a laminar flow down the tracheobronchial tree to the alveoli of the lungs. Because of the changed respiratory epithelium and increased goblet cells, the airflow becomes eddy flow at points of irregularities of the surface. The flow rate decreases in proportion to the irregular surface area. During inspiration, in a normal lung, the airway elongates and narrows. The combined effects of surface changes and changes in the caliber of airways during inspiration, result in decreased air entry in the lungs. During expiration, the elastic recoil of the lung and the chest wall is the sole force, to push air out of the lungs. The force generated by the elastic tissue is directly proportional to the stretched length of elastic fibers. As lungs are less inflated during inspiration, the air low during expiration is reduced. In clinical practice, decreased airflow during expiration is utilized to categorize the degree of severity of chronic bronchitis and is also used as a reliable tool for monitoring the effects of medical therapy. The test is quickly learned by the patients and the gadget costs only a few dollars and is covered by insurance. The test is called Air Flow Meter.

Behind the scenes in the Lab.

In an earlier time, learning about Inflammation and infection was not difficult. With the knowledge of the immunity - innate and adaptive, the role of individual subsets of immunocytes, the importance of cell to cell communication, powerful enzymatic actions of cytokines, bradykinins, chemokines, the role of prostaglandins, interleukins, cellar growth promoting factors, vascular endothelial growth factor, etc. and the role, of the master programmer, the genes and messenger RNA, if not complicated enough, then add gene mutation, age related Telomere gene deletion, point mutations, etc. made medical study akin to study FBI agents receive at the academy.

That aspect is voluminous and better studied under the heading of inflammation, repair and remodeling. In the study of chronic bronchitis, there is no way out other than, at the minimum, to mention some of the processes at critical points of symptom development.

Age and lung function.

At birth, the lung structure and maturity of cells are not fully developed. Lungs continue to grow and cells mature during childhood. Lung growth accelerates during adolescence. By the time the longitudinal growth of the long bone ceases, the lungs also stop growing. The lung is an exceptional organ because it begins to lose function after the mid-20s. It is estimated that an individual loses 1 % of lung reserve each year. Until the loss of volume is greater than 50%, the patients remain asymptomatic. In cigarette smokers, the rate of decline of lung functions is much faster, and they become symptomatic earlier.

In addition, the changes in genes due to age manifest in a variety of ways. Every chromosome has several genes, and each gene has a beginning and end part. The end part of the gene is called Telomere. In advanced age, the telomere portion of the gene is lost. Depending on the gene function, the symptoms vary. Telomere deletion leads to decreased immune functions, specially the repair and remodeling of the lungs.

Symptoms and progression of chronic bronchitis.

Patients become symptomatic after considerable lung damage. Some inhaled chemicals are direct toxins to respiratory cells or due to the generation of free radicals at the local level. Some inherited conditions, like alpha1 antitrypsin deficiency, dyskinesia of ciliary epithelium of the respiratory tract, congenital mitochondrial diseases and macrophage enzyme deficiency, accelerate these changes.

Cough and increased mucoid mucus production are mostly observed in the morning after waking up. Later, more frequent symptoms are noticed during the evening and night. At this stage, the chest x-ray may be negative, but the vital capacity is reduced and also FEV1(expired air volume in the 1^st second of expiration). Similarly, the flow rate is reduced. Frequent respiratory infections due to respiratory viruses are common and occasional bacterial infections are seen.

Each new episode of viral, bacterial infection or exposure to toxins produces destruction of the lamina propria, smooth muscles and elastic fibers.

Repair and remodeling do not progress normally because of repeated inflammations. Haphazard laying down of new cells, generated by the resident progenitor cells of the endothelium, fibroblasts, and myeloblasts, produce irregular remodeling and more obstruction to airflow. Bronchioles less than 2 mm in diameter show a 40 to 50 % reduction of the caliber and can be demonstrated by HTCT (high resolution CT). Loss of elastic fibers distorts the delicate alveoli and capillaries. The surface area of the alveoli is reduced. A mismatch between ventilation and circulation occurs. The arterial oxygen saturation falls during exercise and later at rest. Continuation of infections, abnormal repairs and remodeling produce hypoventilation and Carbon dioxide retention. After each bout of infections,  patients experience progressively worsening shortness of breath.

Chest x-ray shows heavy bronchovascular markings and is in association with patches of infiltrates. Hyperinflation of sub-segmental lobes, most marked in the upper zone of the lungs is seen. Still later, the radiological picture becomes a combination of chronic bronchitis and emphysema. The progression of the disease takes several years. It is not unusual for patients to live with chronic bronchitis for 40 to 50 years. At the final stage, the pulmonary arterial pressure increases in a step-wise fashion in line with the damage to the lung. Right ventricular hypertrophy develops as a compensatory mechanism, and later the right heart fails to keep up and congestive heart failure develops.

 

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Mycobacterium avium-intercellulare

 

                                 Mycobacterium avium-intracellulare complex

                                               PKGhatak, MD

Mycobacterium avium-intracellulare complex (MAC) is a combination of two species of Non-Mycobacterium tuberculosis (NMB). In the past, other NMB species were lumped into this complex.

MAC bacteria exhibit characteristics so very similar and produce almost identical human diseases that the diseases cannot be differentiated clinically and only by the use of genome probe tests actual species diagnosis is made with ease.

MAC is ubiquitous in nature, many MACs are present in water, soil, house dust, plumbing, tap water, etc. Both healthy and immunosuppressed people carry MAC in the respiratory and GI tracts and produce no inflammation or diseases. In fact, it is not easy to establish a pulmonary disease due to MAC unless tissue invasion and recovery of MAC are demonstrable in the biopsy tissues. Person-to-person transmission does not happen.

People with immunosuppression are living longer and the incidence of MAC infection is rising. HIV infected patients, until recent years, were devastated by MAC and are still susceptible to M. avium infection. Elderly women are particularly susceptible to M.intercellulare. The actual reason for their susceptibility is not known. It was thought that modesty in earlier English women prevented them from coughing in public, resulted in retaining sputum in the airways and that was responsible for repeated infections and the development of nodular bronchiectasis. This is known as Lady Windermere syndrome.

In rare instances, multiple family members develop cervical lymphadenitis by MAC due to congenital deficiency of IFN-y receptor expression or the gene. Patients with gastroesophageal reflux, gastric acid suppression by medications and gastric aspirations are susceptible to M.intercellulare pulmonary infection. Globally MAC is a major problem in poor nations where MTB is common and often MAC are misdiagnosed as drug resistant MTB. In France, New Zealand, and the U.K. MAC incidence is increasing.

Manifestations of MAC infection.

The clinical picture is better described under immunocompetent and in immunosuppressed populations.

In immunocompetent people.

These manifestations are encountered – Cavitary pulmonary infection, Nodal bronchiectasis and Hypersensitive pneumonitis. And cervical lymphadenitis in children.

Cavitary pulmonary infection.

The clinical picture of this entity is similar to M.kansasii infection. The only way to differentiate between the two is to use a newer species identification test like a genome probe test.

Similarly, the clinical pictures of nodular bronchiectasis and hypersensitive pneumonitis are similar to M. kansasii infection.

MAC can infect children. Cervical lymph nodes are commonly infected. In a rare instances, other lymph nodes in the axilla, hila of lungs and groin are infected.

Extrapulmonary MAC infection sites are flat bones, breasts, bone marrow, skin, muscles, brain, and GI tract in immunosuppressed people.

Pulmonary manifestations of MAC.

In an immune competent.

Cavitary pneumonia, nodular bronchiectasis, hypersensitive pneumonitis.

In children with cervical lymph nodes.

In immunosuppressed people.

Multi-organ infections besides lungs are bone marrow, spleen, retroperitoneal lymph nodes, kidneys, liver and occasionally brain and meninges.

Diagnosis of MAC.

Chest Radiographs.

The chest x-ray is not sensitive enough to an early diagnosis of MAC. High-resolution CT scan (HRCT) shows the lesions much more clearly. Fibro-cavitary changes in the upper lung zones. In elderly women, fibronodular bronchiectasis and nodules in the right middle lobe. In addition, atelectasis, consolidation, ground-glass opacities on CT appear as a tree in early spring with the emerging buds – Tree-Bud appearance. In hypersensitive pneumonitis, centrilobular nodules, ground-glass opacities, and hyperinflation coalesced alveoli due to trapped air during expiration indicating expiratory bronchial obstruction.

In HIV patients abdominal CT reveals retroperitoneal and periaortic lymphadenitis, enlarged spleen, and liver.

Biopsy.

Infected tissues are biopsied by a method suitable to patients in order to minimize tissue damage by the biopsy process. Commonly bronchoscopic transbronchial lung biopsy is practiced. Other methods are CT-guided needle biopsy, Transthoracic video assisted tissue biopsy and open lung biopsy.

Culture for MAC.

Blood, urine, pus, lung tissue, node biopsy, bone marrow, and liver biopsy tissues are stained by Ziel Nielsen stain for Acid-fast bacteria (AFB) and cultured in rapid growing culture media.

In tissues with only a few AFB Nuclear, acid amplification tests followed by genome probe tests are done.

Histology.

In HIV positive cases, inflammatory nodes are few, but AFB is plentiful and appears as sheets of macrophages loaded with AFB.

Cervical lymph nodes.

Both caseating and non-caseating granuloma with sinuous tracts of eosinophilic necrosis and scatted nuclear debris are present. Langhans giant cells surrounding nodules are easily identified and neutrophils are rare and lymphocytes are few. AFB is present in a few numbers.

In immunocompetent patients.

Typical non-caseating granuloma and significant numbers of AFB are present.

Treatment.

Drugs used in Pulmonary tuberculosis (MTB) are generally resistant in MAC cases.

Macrolides are the mainstay of therapy, at minimum three drugs are prescribed for 12 months. The usual protocol includes macrolides. rifamycin and ethambutol. Other drugs with variable effectiveness are clofozinidine, fluoroquinolones, aminoglycosides, and inhaled liposomal amikacin.

Various combinations of drugs are used based on the sensitivity test results and response noted in a patient. From treatment centers to nurse-observed intermittent therapy is used to maximize effectiveness and compliance.

Surgery.

Cervical lymphadenitis is best treated with surgical excision. In general, drug treatment is not required.

In resistant pulmonary MAC, lobectomy may be required, in addition to a maximum tolerable dose of drugs.

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Mycobacterium kansasii infection

 

                                      Mycobacterium kansasii infection

                                         PKGhatak, MD

Mycobacterium kansasii is a harmless mycobacterium for healthy people. It is a different picture for people with long standing chronic lung diseases like cystic fibrosis, alpha1 antitrypsin deficiency and immune depressed people because of HIV infection, autoimmune diseases, or under medical treatment for cancer, etc.

Mycobacterium kasasii (M.kansasii) belongs to a group of mycobacteria known as NMB (non-mycobacteria tuberculosis) which is distinct from MTB responsible for Pulmonary tuberculosis.

Mycobacterium kansasii.

M.kanasasii are acid fast, slow growing NMB. The colony produces an orange colored smooth colony when grown on solid media and exposed to light. In the dark, the colony is colorless and rough. It tests negative for niacin and positive for catalase and has other similar biochemical features of NTBs. M. kansasii, unlike other NTM, is not universally present in soil and water, and colonization of the respiratory tract in healthy adults is a rare event. In addition to infection of the lungs, M. kansasii also infects vertebrae, bone marrow, spleen, liver, muscles, and skin.

In the USA, the incidences of new cases of M. kansasii are increasing as the mycobacteria tuberculosis infections are declining.

Texas recorded the most new cases of M.kansaii followed by Louisiana and Florida. As the name implies, M.kansasii is prevalent in Kansas and also seen in the adjoining mid-central states. White populations are more susceptible to M. kansasii infection.

Globally - the miners in South Africa have high rates of new infections, and also in Wales, UK.

Two groups are commonly infected -adults with underlying conditions and children between 4 and 6 years old, along with young adults.

Pulmonary diseases due to M. kansasii.

Three distinct clinical presentations are recognized

 1. Cavitary pulmonary tuberculosis.

 2. Nodular bronchiectasis.

 3. Disseminated infection.

The incidence of hemoptysis is 30%, weight loss is about 50%, and chest pain is seen in 25% of cases. Other symptoms like cough, production of sputum, fever, etc. have no specificity to this infection. Children and young adults present with cervical adenopathy in addition to pulmonary infections.

X-ray features. A single or multiple thin walled cavities in the apical portion of the lungs and hilar lymph node enlargement in association with bilateral pulmonary infiltrates are seen. In patients with severely depressed CD4 cell count, localization of the infection or cavity formation does not happen and dissemination of disease is usual. These findings along with a positive acid-fast organism in the sputum nearly clinch a clinical diagnosis of NMB infection.

Nodular bronchiectasis.

Inflammatory reactions and tissue destruction produce a weakened wall of smaller size bronchial tubes result in the development of multiple nodule shaped bronchiectasis in the central lung field. Frequent bouts of productive cough with streaks of blood along with other symptoms of infection are usually present. Secondary fungal and bacterial infections are frequent occurrences.

Disseminated infection.

Disseminated infection is mostly present in severely immunosuppressed patients. Bides lungs, bones, spleen, subcutaneous tissues, and kidneys are infected.

The sputum and bronchial washings should not be treated with KOH in the laboratory (a normal practice), because KOH kills M. kansasii and no growth will result in culture. Rapid liquid culture media should be used in growing M. kasasii, a growth in 2 weeks is expected. Newer techniques of species identification should be done. These tests are the Molecular hybridization test, PCR restriction analysis, Nucleic acid amplification test, Restriction fragment length polymorphism, Polymorphic tandem repeats, DNA genomics probe, etc.

Species identification not only speeds up identification but is also used as a guide in the selection of anti-tubercular drugs.

Non-pulmonary M.kasasii infection.

Cervical lymphadenitis in children is primarily due to M. tuberculosis followed by M. bovis. Of the NTM, the M. avium complex infection predominates. M. Kansasii cervical adenitis is the next common cause of childhood cervical adenopathy. The submandibular, submaxillary nodes are primarily involved but the submental, preauricular and periauricular glands are also infected. The skin over the enlarged glands appears glossy, the glands feel rubbery to touch. Often the swollen glands rupture and produce chronic discharging sinus tracts. Many children have a low grade fever, anorexia and fail to gain weight.

Osteomyelitis of the spine and sacroiliac.

The flat bones are susceptible to infection due to a rich blood supply. Often pain and fever are followed by abscess formation. In lower thoracic and lumbar vertebra osteomyelitis the abscess drains down the psoas fascia to the groin and can rupture producing a pus draining sinus tract.

When the spleen is infected, generally an abscess forms and patients can present as a fever of unknown origin. Liver, bone marrow granulomas and skin lesions are seen. Rarely, a meningoencephalitis develops.

Non-pulmonary infections are more common following a hematogenous spread and HIV infected people with CD4 cell counts below 50 are susceptible to these complications.

Diagnosis.

Biopsy tissues. All biopsied tissues should be stained for acid fast and cultured. Identification should be augmented by the newer methods listed above. Fungal and bacterial cultures are done at the same time.

Lymph nodes and bone marrow typically show several noncaseating granulomas with variable numbers of acid-fast organisms.

In disseminated M.kasasii infection blood culture, urine and bone marrow cultures usually show growth in 2 weeks. All positive cultures are tested for drug resistance.

Treatment.

M.kansasii are resistant to pyrazinamide and resistance to INH & Rifampin is increasing. The initial anti-tubercular medications include INH, Rifampin, and Ethambutol. If M.kansasii is resistant to any 1^st line drugs, then Azithromycin, Fluoroquinolones, Sulfamethoxazole, and Streptomycin are added in various combinations.

Complications. Pleural effusion is a rarity, pneumothorax is occasionally seen.

Treatment of cervical adenitis.

Early surgery should be done and is a very effective way to cure. In advanced cases with draining sinus tracts, treated with anti-tubercular medications for 3 to 6 months, followed by surgery.

Mortality and morbidity vary according to the extent of the disease at the time of presentation and the immunological status of patients.

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Clinical Presentation of Pulmonary Tuberculosis

                                    Clinical Presentation of Pulmonary Tuberculosis

                                                PKGhatak, MD

Pulmonary Tuberculosis presents in multiple ways.

Pulmonary tuberculosis is a very old disease. Evidence of tuberculosis was detected in 4,000 old Egyptian mummies. Description of TB like disease was recorded in 3,500 old Sanskrit literature, and still, older evidence was uncovered in Israel in a skeleton found in an old grave. Currently, pulmonary tuberculosis is still very much prevalent globally and is a curse for people of Southeast Asian and Northern African countries. 10,000 new cases were detected worldwide and 1.5 million people died of tuberculosis in 2018.

Pulmonary tuberculosis has several modes of presentation. The clinical presentations of clinical illness due to TB vary according to the prevailing standard of sanitation and public health of countries.

Latent Tuberculosis in Western countries.

Immigrants coming to Western countries require a negative chest x-ray as a prerequisite for a visa. Tuberculosis (TB) tests are mandatory in many countries for employment in schools, universities, hospitals, healthcare, nursing homes, and would be new nursing home residents and workers in the retail business. Some of the applicants react positively to the Interferon gamma release blood test or the old fashioned TB skin test.

These positive TB-tested people are completely symptom free, have no indication of prior TB infection, and are unable to recall coming in contact with an infectious TB patient.

Recently, a new method has been described to identify active tuberculosis from latent infection by determination of IL-8.IL-18, and IL-33 in TB-antigen stimulated of the whole blood with 85 % accuracy.

A careful review of a recent chest x-ray or CT chest will identify a small nodule in the upper part of the lungs, and also occasionally a small regional calcified lymph node. Induced sputum smears and cultures are done routinely and are negative.

The Public Health Department (PHD) must be notified and state mandated treatment protocol and follow up are taken up by the PHD.

Reactivation of Latent TB.

Two ways the reactivation of latent TB presents

 1. Local spread,

 2. Pleural effusion.

Local spread.

Many immigrants from countries where TB is prevalent may not be subjected to TB surveillance upon arrival in the new country. They remain symptoms free for a very long time until the cellular immunity is reduced by an infection like HIV, and immunosuppressed conditions due to Diabetes mellitus, prolonged use of corticosteroids, immunosuppressed drug therapy in organ transplants, and cancer chemotherapy. The dormant TB bacteria residing within the macrophage cells wake up and become metabolically active and begin to multiply. Eventually, TB bacteria break up the cellular barrier and invade adjoining tissues.

As TB becomes an active disease the patient may experience profuse night sweats, unproductive cough, evening chills and a low grade fever and loss of weight.

The clinical examination, followed by laboratory tests, reveals a positive Interferon gamma release assay (IGRA) and a single pulmonary nodule in the upper zone of the lung in the CT chest. These abnormal shadows often show two distinct densities - a denser central core and a lighter peripheral cellular infiltrate zone 

The major concern at this stage is – it is cancer or granuloma. TB bacteria are one of the few other microscopic organisms that produce granulomas.

The most direct way to distinguish between the two is to obtain tissue by a skinny needle biopsy with ultrasound/ fluoroscopic guidance.

But if the granuloma is due to TB infection, that might contaminate the path of the needle and might help to spread TB to the pleura and subcutaneous tissues.

The alternative is to wait 3 to 6 months and obtain a repeat CT scan and then evaluate the activity of the lesion and then decide when to biopsy.

This decision must depend on the best judgment of the attending physician and the patient. There are risks both ways.

Induced sputum for cytology for cancer, fungal, and TB is also performed as a part of the initial evaluation. Depending on the culture media used for TB culture, positive growth may or may not be available in 4 to 6 weeks. Bronchoscopic brushing and washings are examined for cancer and infectious agents. The success rate of identifying cancer/ infection is better by examining the bronchoscopy materials, but the success rate is not 100 %. The IGRS test of bronchial brushing and wash fluid containing mononuclear cells has a much higher rate of positivity of IGRS compared to peripheral blood lymphocytes.

Pleurisy and Pleural Effusion.

Clinical presentation.

The onset of chest pain, fever, and mild non-productive cough suddenly occurs in young apparently young healthy individuals. Pleural space TB inflammation takes place in one of the two ways - hypersensitive reaction and direct infection.

Hypersensitive reaction.

It is the usual mode. The initial symptom is a sudden onset of chest pain aggravated by breathing. The two layers of pleura, rubbing against each other during inhalation and produce chest pain. A few days or weeks later the pain suddenly diminishes once the pleural fluid begins to accumulate. Then the patient feels heaviness in one side of the chest and may develop a low grade persistent fever.

In the pleuritic state, audible friction rubs on auscultation are diagnostic of pleurisy but not diagnostic of TB pleurisy only. The right sided pleural effusion is usually seen and less than 10 % of cases of TB pleural effusion may be bilateral. The pleural fluid is easily obtained by bedside thoracentesis, at the same time pleural biopsy is performed by a special needle (Abram's needle). A pleural biopsy is safe because the lung is separated from the pleura by a layer of fluid and the chance of pneumothorax is minimal.

The TB pleural fluid is light yellow in color, the protein content is over 3 gm/dL, cell count 100 to 1000 /ml and predominantly lymphocytic, glucose content is less than 40 mg/dL, ADL (adenosine deaminase) test on T-lymphocytes is typically over 45U/L but below 200U/L. The ADL is the most sensitive (93%) and specific test (94%) for TB pleural effusion. IGRA assays are specific, but sensitivity is 70% in the peripheral blood and 97% in pleural fluid lymphocytes. TB culture grown in liquid media is in the 50 % range. TB bacteria in smears are rarely seen in hypersensitive TB pleurisy/pleural effusion. In hypersensitive pleural effusion, a pleural biopsy may or may not show caseating granuloma. If granuloma is present, then a few TB bacteria can be identified in pleural TB infection.

TB infection of Pleura.

A subpleural TB nodule ruptures in the pleural space. The escaped TB bacteria infect the pleura. Occasionally the TB bacteria are carried into the pleural space by the lymphatics. The contamination of the pleura in one way or another results in pleurisy and pleural effusion. The clinical presentation, however, is a bit different. Here, any age group of people may be infected, except children. The patients are ill if they have progressive primary pulmonary TB infection. In latent TB patients, most patients are symptom free prior to pleural effusion. A short period of pleuritic chest pain followed by pleural effusion occurs, like the hypersensitive pleural effusion.

Chest X-ray reveals, in addition to pleural effusion, the site of latent TB infection.  The character of pleural fluid is no different from the hypersensitive pleural effusion and additionally, RBCs in variable numbers are present. The pleural biopsy reveals caseating granulomas and TB bacteria are generally identified in the granuloma. The smear of the fluid may not show TB bacteria, but cultures in liquid media are always positive. If the TB bacteria are scanty, they can be identified by Nucleic Acid Amplification Test (NAAT)

Primary Pulmonary Tuberculosis.

Primary pulmonary tuberculosis is a global health problem. People in every country of the globe are contracting pulmonary tuberculosis every year.

Two factors have made tuberculosis eradication a daunting task. 1. TB bacterial survival resiliency. 2. Handicapped immune system to fight TB infection. Human TB bacteria that produce primary pulmonary tuberculosis are called Mycobacteria Tuberculosis, in short MTB.

MTB survival resiliency.

MTB are rod shaped, nonmotile, slow growing bacteria and need oxygen to grow. It lives inside Macrophages and multiplies under favorable conditions. MTB has a three-layered cell wall. The multilayered cell wall blocks TB drugs to enter the bacterial body in sufficient concentration to kill the MTB.

Handicapped Immunity.

In any infection, both the Cellular and Humoral immune systems are activated. But in MTB infection the Humoral immunity remains largely inactive. The CD4 cells, macrophages and other immune T-cells collectively fight against MTB invasion.

Mode of MTB primary pulmonary infection.

 MTB is a respiratory pathogen, human to human transmission occurs via infected droplets. Causal contact with an open MTB case (TB bacteria in sputum) does not cause infection; prolonged contact and repeated exposures over months are necessary. Overcrowded prisons, sailors in submarines, residents in dormitories, hostels and nursing homes are ideal places for MTB transmission.

A majority of inhaled droplets are caught by the mucociliary escalator and are eliminated. A few MTB reaches the alveoli. MTB penetrates the alveolar wall and enters the interstitial tissues and is promptly caught and swallowed by the tissue macrophages. Macrophages are unable to digest the MTB due to the presence of enzymes in bacteria that neutralize the digestive enzymes of macrophages, and the bacterial wall is indigestible. Additional macrophages and lymphocytes accumulate around the infected macrophage and a nodule is formed. 85 % of the initial infections are contained and confined locally. But MTB remains dormant inside the infected macrophages. This infected nodule becomes Latent TB.

Progressive Pulmonary TB.

People with suppressed cellular immunity are unable to limit the initial infection. The MTB multiplies and break out of macrophages and infect the adjoining areas, some of the infected macrophages carry the bacteria to the regional lymph follicles/nodes and these two infected areas are collectively called the primary complex. Further growth and progression of infection continue. 6 to 9 months after the initial infection the patient starts to experience symptoms.

In advanced countries, only 1/3 of newly diagnosed cases are due to fresh infections and the rest 2/3 are due to the reactivation of latent TB.

Symptoms are - lack of energy, easy fatigue, anorexia, loss of weight, short but successive unproductive coughs and profuse night sweats are common.

Further progression of the disease produces: 1. Wide areas of Pulmonary infection and is known as primary progressive Tuberculosis. 2. Hemoptysis. 3. Miliary TB.

Primary Progressive Pulmonary Tuberculosis.

These patients are sick and weak. Persistent low grade fever, wasting of muscles, anemia, cough productive mucopurulent sputum and occasional streaks of blood in sputum is present. Confirmation of pneumonia is not difficult but there are no special clinical features of MTB pneumonia.

Chest x-ray shows infiltration in the upper zone of the lung, usually on the right side and spread of the disease in the adjoining lobes. In some cases, thick walled cavity is seen in the upper lobe or apical portion of the middle lobe. In nursing home patients, middle lobe and lower lobe infiltrations are common.

Sputum smears and cultures are the cornerstones of MTB diagnosis. IGRA assay of peripheral blood is both sensitive and specific. In occasional cases, NAAT (Nucleic acid amplification) test may be necessary.

Hemoptysis. Blood-streaked sputum is an indication of the progression of disease and destruction of the lungs. That leads to bringing up frank red blood.

Almost all patients present with hemoptysis undergo bronchoscopic examination. It not only helps to diagnose MTB but also eliminates the possibility of lung cancer and fungal infection.

Miliary Tuberculosis.

MTB not only destroys the lung parenchymal tissues but also penetrates blood vessels and spreads far and wide. MTB can also spread via lymphatics. The tissues rich in oxygen support further MTB growth. Lungs, meninges, bone marrow, and kidneys are common sites of extrapulmonary TB infection.

The patients are very malnourished, very weak and unable to cough properly. Sputum production is generally absent or minimal. Patients are febrile and may show abnormal liver, renal functions and electrolyte imbalance. Both acute and chronic phase reactants are positive. In severely immunosuppressed patients with low CD4 cell count, the TB skin tests and IGRS test may be negative.

The chest x-ray is virtually diagnostic, and a bone marrow biopsy showing granulomas and MTB are easily demonstrated. Bone marrow cultures are necessary for the final diagnosis and also for the detection of drug resistance. Concurrent HIV infection must be eliminated by proper tests.

All Pulmonary MTB cases must be reported to the local Public Health Department (PHD). PHD use approved treatment protocol, makes sure of TB drug delivery and compliance of patient in taking TB drugs, and performs contact tracing and chemoprophylaxis of appropriate people.

In addition to these modes of presentation of MTB pulmonary infections, some unusual presentations are also identified in unsuspected patients on bronchoscopy. The use of more advanced tests helps to identify MTB infections. That part is not discussed here.

Non-MTB mycobacterial pulmonary infections are less common but the number of new cases is growing. This subject is discussed in a separate place.

edited May 2025

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Metal Fumes and Lung Diseases

 

                                              Metal Fumes and Lung Diseases

                                                 PKGhatak, MD

People do not encounter metal fumes every day, and many may be completely unaware of them. It is a different story for factory workers, foundry workers, ironworkers, and workers in many other workplaces where exposure to metal fume inhalation is a daily occurrence.

Lungs are exposed to the environment directly; whatever is in the air it finds its way eventually into the lungs. The gastrointestinal tract is very well protected by a layer of very strong acid secreted by the stomach, the skin is impervious to most agents to a certain degree, and the eyes are partially protected by tear secretion.

Reactions of the lung to metal fumes.

Metals used in industries and household products come in several forms. The metals may be in the pure metallic form, combined with other elements like oxide, sulfide, nitrite, halide, carbide and also combined with organic compounds. For these discussions, all are simplified as metals. Also, important to point out that the toxicities not only vary from compound to compound but also in the frequency of exposure and concentration in the air. The solubility of metal compounds influences pulmonary reactions; poorly soluble compounds are caught and eliminated by the mucociliary escalator, and soluble compounds react with tissues directly and produce more intense reactions.

Certain metal fumes produce only minimal fibrosis in the lung; the metal merely fills up the lung. An example is iron.

The inhalation of nickel and beryllium produces intense inflammation, leading to extensive fibrosis of the lungs.

Many other metals may produce reactions between these two reactions.

In some cases, the metals combine with the protein of the body and become antigenic and producing immune reactions. These metals act as Heptane, for example, platinum, chromium, cobalt, etc.

Some metals produce only one type of pulmonary disease, others, like chromium, produce several different clinical diseases.

Clinical conditions produced by metal fumes.

1. Cadmium, Lead, Zinc, and Chromium:

2. Nickel, Chromium, and Cobalt:

Acute bronchitis, chronic bronchitis, and sinusitis are common occurrences.

Occupational asthma.

3. Platinum:

Hypersensitive pneumonitis.

4. Iron, Tin, and Barium:

Pneumonitis without fibrosis.

5. Beryllium, and occasionally Tin and Aluminum'

6. Barium and Antimony.

Pneumonitis with fibrosis.

7. Cadmium:

Pulmonary emphysema.

8. Baetllium, Tin and Aluminium:

Granulomatous lung disease is similar to sarcoidosis.

9. Cobalt:

Desquamative giant cell interstitial pneumonitis.

10. Radium and Iron:

Lung cancer.

11. Lithium, Zinc, and Lead:

Pulmonary edema.

12. Zinc and Lead:

Chronic obstructive pulmonary disease.

13. Aluminum:

Alveolar Proteinosis .

In addition to lung diseases, metals also produce liver, kidney, and other organ damage. Those are not discussed here.

Professions outside metal manufacturing are susceptible to pulmonary diseases.

Diamond polisher – exposure to cobalt.

Aerospace industries – exposure to beryllium.

Electronic, computer, and ceramic – exposure to beryllium.

Dental technicians – exposure to align, beryllium.

Housewife/spouse (workers bringing home) - beryllium dust in their clothing.

Painters – pigments containing various metal compounds.

Boilermakers and Oil tanker cleaners - exposure to vanadium.

Firework and explosive makers - exposure to aluminum.

Hard metal toolmakers and users - exposure to tungsten

Chrome plating – exposure to chrome.

Glass polishers and lens makers - exposure to cerium (rare earth).

How metals act in tissues:

1. Metals like iron, copper, magnesium, cobalt, and zinc are coenzymes in many enzyme systems.  2. Many transport proteins are compounds of metals. 3. Some metals readily combine with proteins and sensitize immune cells. 4. Metals combined with macromolecules hinder DNA repair.

2. The incidence of inhaled metal compounds and pure metal fumes is increasing due to the expansion of manufacturing facilities near residential districts and the relaxation of air quality standards in recent years.

3. The lung diseases caused by metal fumes have no easily distinguished features from usual chronic lung conditions like chronic bronchitis or pneumonitis, and pneumonia. People are well aware that lung cancer and COPD are related to cigarette smoking. However, many nonsmokers develop COPD and lung cancer, and they are baffled and ask their doctors what caused their illness.

It is only by a careful and detailed history of occupation, home environment, recreation, and hobby habits that a cause can be identified.

Tests for the identification of metals:

1. High Performance Liquid Chromatography. And Gas Chromatography.

The final identification depends on the demonstration of that metal in the respiratory tissues or secretions, or bronchial washing fluid, by one of the two tests mentioned above.

2. Immunoassays.

3. The specific antibodies against the suspected metal tests are available, but are not as sensitive and specific as chromatography.

 edited May 2025.

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Black Lung Disease

 

                              Black Lung Disease / Coal Miners Pneumoconiosis

                                           PKGhatak,MD

Coal dust was thought to be inert particles, but now it is well established that inhaled coal dust is responsible for black lung disease. The accumulation of coal dust in the lungs and the tissue reactions to its presence produce black lung disease.

Coal dust of 4 μm size or smaller can easily reach the alveoli, bypassing the mucociliary defense of airways. The small dust particles penetrate the alveolar membrane and travel via lymphatics to the local lymph nodes. Macrophages in the interstitial tissue of the lung engulf coal particles, but macrophages can not digest coal. Coal laden macrophages release cytokines. The cytokines cause inflammatory reactions. The accumulated macrophages form a small, tiny flat collection of cells called macules. The macules are found in the upper lobes of the lungs. Later the macules coalesce to form nodules due to fibrosis. The fibrous tissues distort bronchioles and result in focal emphysema. Initially, the fibrosis may be localized but becomes diffuse when coal dust exposure continues.

The incidence of back lung disease is increasing in the USA due primarily to the relaxation of laws and regulations, over the years, limiting coal dust exposure to miners. Because of the wider use of coal in developing countries for electricity generation, global incidence is on the rise.

This is a major setback for those physicians, attorneys, social workers, researchers and others who worked so hard for so many years in hostile environments, created and financially supported by the management/investors, at the cost of the health and welfare of miners and their families.

In the USA, the incidence of Black Lung Disease among coal miners is -

In 1975 - 32 cases / 1000 miners were diagnosed with black lung disease.

In 1980 - 13 cases / 1000.

In 1990 - 25 /1000.

In 2000 - 3.7 / 1000.

In 2010 - 19 /1000.

In 2015 - 51 / 1000.

Types of Coal and Black Lung Disease.

Anthracite coal is hard coal, it has 84 % of carbon and contains less volatile compounds. It is also the worst coal for the development of black lung disease. In Pennsylvania coal towns -Scranton and Wilkes-Barre area, where coal mines were the main employers, the incidence of black lung was 10 % in miners exposed to coal dust over 25 years. Since anthracite coal is exhausted from this area, the mining companies switched to Bituminous coal mining. Bituminous coal is abundant in West Virginia, Kentucky, and Pennsylvania. Bituminous coal is soft, and it is less harmful to the lungs.

Cigarette smoking does not directly exacerbate fibrosis but chronic bronchitis and emphysema secondary to smoking worsen the coal miners' symptoms.

The inhalation of coal dust is usually accompanied by the inhalation of silica dust. The coal seams are embedded in between the layers of hard rocks and had to be blasted off. That generates a cloud of dust in the underground mines due to poor ventilation. The silica and coal dust in large quantities are inhaled. At present, the practice of blasting off the top of mountains to reach the coal seams is also causing huge dust clouds. That is not only inhaled by miners but also by their children and other family members.

  

               Black lung.

Clinical presentation.

In early cases, the patients may have no symptoms but chest X-rays show multiple small lung nodules in the upper lobes of the lungs. In more advanced cases the apical portion of the middle lobe is also involved and the shows become more profuse. As the disease advances further the fibrosis becomes more diffuse. And lower lobes also show changes. In addition, pulmonary emphysema and cavities of different sizes may be present. This stage of the illness is called Progressive pulmonary Fibrosis.

In patients with Rheumatoid arthritis, subpleural cavitary nodules are seen. This is known as Caplan syndrome

Symptoms.

There are no specific symptoms of back lung disease. Cough, and sputum production containing black dust may be present. Shortness of breath, exhaustion and weight loss and limitation of physical activities are usual and at this stage patients are disabled.

Disability Determination.

Federal and State laws developed over years, and their criteria are well described in publications. The criteria were developed based on

    1. Type and size of shadows in the x-rays.

    2. The percentage of lung area affected in relation to the whole lung.

3. The degree of pulmonary function test abnormality

4. Under saturation of Oxygen detected during a standard exercise. A detailed description of this subject can be obtained in the State Coal miners disability acts.

Complications.

Pulmonary hypertension and right heart failure and cardiac arrhythmia eventually develop. The lung cavities invite bacteria. Mycobacterial tuberculosis infections often coexist. Mycobacteria tuberculosis and atypical mycobacterial infections produce accelerated fibrosis.

Treatment.

Once the black lung disease is well established, the reversal of the disease is not possible. Treatment is directed toward controlling the secondary complications. The standard therapy for pulmonary emphysema and chronic bronchitis, heart failure and respiratory insufficiency are undertaken depending on the cases.

Prognosis.

In the USA 1,500 die each year from black lung disease and 25,000 globally.

[ Nomenclature:

Pneumoconiosis is a Greek word meaning dust disease of the lung. Pneuma= wind, kons= dust.

Black lung disease is known as Anthracosis in Greek / medical literature. Anthraco means coal.]

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